MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Annals of Human Genetics' source. Thu, 09 Feb 2012 09:43:27 +0100 http://www.medworm.com/index.php?rid=5615578&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00700.x SummaryThere are four tests – the likelihood ratio (LR) test, Wald's test, the score test and the exact test – commonly employed in genetic association studies. On comparison of the four tests, we found that Wald's test, popular in genome‐wide screens due to its low computational demands, exhibited a paradoxical behaviour in that the test statistic decreased as the effect size of the variant increased, resulting in a loss of power. The LR test always achieved the most significant P‐values, followed by the exact test. We further examined the results in a real data set composed of high‐ and low‐cholesterol subjects from the Dallas Heart Study (DHS). We also compared the single‐variant LR test with two multi‐variant analysis approaches – the burden test and the C‐alpha tes... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5615578 Sun, 01 Jan 2012 05:00:00 +0100 5615578 http://www.medworm.com/index.php?rid=5602572&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2012.00699.x SummaryOur aim was to investigate whether the ADIPOQ gene polymorphisms are associated with the metabolic syndrome (MetS). Genotypes of MetS patients (n= 1049) and normal controls (n= 1092) were analysed by TaqMan® assay, and serum adiponectin concentration was measured by ELISA. The variant genotypes rs266729CG; rs1063539GC, GC/CC; rs16861205AA and rs7649121AT, AT/TT (Adjusted P= 0.037, 0.044, 0.025, 0.011, 0.019, 0.020, respectively) of the ADIPOQ gene were associated with MetS. Patients with rs266729CG, CG/GG genotypes (P= 0.034, 0.035) and rs7649121AT, AT/TT genotypes (P= 0.013, 0.022) had higher levels of serum adiponectin than those with the CC and AA genotypes respectively. Furthermore, the prevalence of haplotypes GGAAAATC and GGGTAACC was lower in cases (10.7% and 4.5%) than in c... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5602572 Sun, 01 Jan 2012 05:00:00 +0100 5602572 http://www.medworm.com/index.php?rid=5590830&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00698.x SummaryA genome‐wide association study of serum uric acid (SUA) laevels was performed in a relatively isolated population of European descent from an island of the Adriatic coast of Croatia. The study sample included 532 unrelated and 768 related individuals from 235 pedigrees. Inflation due to relatedness was controlled by using genomic control. Genetic association was assessed with 2,241,249 single nucleotide polymorphisms (SNPs) in 1300 samples after adjusting for age and gender. Our study replicated four previously reported SUA loci (SLC2A9, ABCG2, RREB1, and SLC22A12). The strongest association was found with a SNP in SLC2A9 (rs13129697, P= 2.33×10−19), which exhibited significant gender‐specific effects, 35.76 μmol/L (P= 2.11×10−19) in females and 19.58 μmol/L (P= 5.40×1... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5590830 Sun, 01 Jan 2012 05:00:00 +0100 5590830 http://www.medworm.com/index.php?rid=5567023&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00696.x In this study, seven SNPs (WEX28 rs17312728:G>T, WEX70 rs45631657:C>T, WEX1 rs10521868:A>C, ATL1 rs4949:A>G, FMRb rs25707:A>G, WEX17 rs12010481:C>T and WEX10 ss71651741:C>T) have been analyzed in two Basque valleys (Markina and Arratia). We examined the association between these SNPs and the CGG repeat size, the AGG interruption pattern and two microsatellite markers (FRAXAC1 and DXS548). The results suggest that in both valleys WEX28‐T, WEX70‐C, WEX1‐C, ATL1‐G, and WEX10‐C are preferably associated with cis‐acting sequences directly influencing instability. But comparison of the two valleys reveals also important differences with respect to: (1) frequency and structure of “susceptible” alleles and (2) association between “susceptible” alleles and S... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5567023 Sun, 01 Jan 2012 05:00:00 +0100 5567023 http://www.medworm.com/index.php?rid=5531245&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00695.x SummaryModern humans originated in Africa before migrating across the world with founder effects and adaptations to new environments contributing to their present phenotypic diversity. Determining the genetic basis of differences between populations may provide clues about our evolutionary history and may have clinical implications. Herein, we develop a method to detect genes and biological processes in which populations most differ by calculating the genetic distance between modern populations and a hypothetical ancestral population. We apply our method to large‐scale single nucleotide polymorphism (SNP) data from human populations of African, European and Asian origin. As expected, ancestral alleles were more conserved in the African populations and we found evidence of high divergence... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5531245 Fri, 23 Dec 2011 03:24:57 +0100 5531245 http://www.medworm.com/index.php?rid=5531247&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00693.x SummaryIn principle mutational records make it possible to estimate frequencies of disease alleles (q) for autosomal recessive disorders using a novel approach based on the calculation of the Homozygosity Index (HI), i.e., the proportion of homozygous patients, which is complementary to the proportion of compound heterozygous patients P(CH). In other words, the rarer the disorder, the higher will be the HI and the lower will be the P(CH). To test this hypothesis we used mutational records of individuals affected with Familial Mediterranean Fever (FMF) and Phenylketonuria (PKU), born to either consanguineous or apparently unrelated parents from six population samples of the Mediterranean region. Despite the unavailability of precise values of the inbreeding coefficient for the general popul... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5531247 Wed, 21 Dec 2011 05:00:00 +0100 5531247 http://www.medworm.com/index.php?rid=5531246&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00694.x SummaryFragile X syndrome (FXS) is characterized by moderate to severe intellectual disability, which is accompanied by macroorchidism and distinct facial morphology. FXS is caused by the expansion of the CGG trinucleotide repeat in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene. The syndrome has been studied in ethnically diverse populations around the world and has been extensively characterized in several populations. Similar to other trinucleotide expansion disorders, the gene‐specific instability of FMR1 is not accompanied by genomic instability. Currently we do not have a comprehensive understanding of the molecular underpinnings of gene‐specific instability associated with tandem repeats. Molecular evidence from in vitro experiments and animal mod... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5531246 Wed, 21 Dec 2011 05:00:00 +0100 5531246 http://www.medworm.com/index.php?rid=5519543&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00691.x In conclusion, this meta‐analysis supports that the MTHFR A1298C polymorphism is capable of causing male infertility susceptibility, especially azoospermia. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5519543 Tue, 20 Dec 2011 02:29:52 +0100 5519543 http://www.medworm.com/index.php?rid=5519542&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00687.x SummaryMethylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD). The aim of this study was to investigate the relationship of the MTHFR C677T polymorphism with the risk of CHD in children with CHD and their parents by meta‐analysis. Studies were identified by searching electronic literature for papers before 2011, focusing on MTHFR C667T and the risk of CHD. All data were analyzed using the fixed effects model in Cochrane Review Manager 5.1.1. Twenty eligible case‐control and family‐based studies were included. Overall analysis yielded pooled odds ratios (OR) of 1.55 (95%CI 1.25–1.9... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5519542 Tue, 20 Dec 2011 02:29:49 +0100 5519542 http://www.medworm.com/index.php?rid=5446385&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00690.x SummaryThe eastern Himalayas are located near the southern entrance through which early modern humans expanded into East Asia. The genetic structure in this region is therefore of great importance in the study of East Asian origins. However, few genetic studies have been performed on the Sino‐Tibetan populations (Luoba and Deng) in this region. Here, we analyzed the Y‐chromosome diversity of the two populations. The Luoba possessed haplogroups D, N, O, J, Q, and R, indicating gene flow from Tibetans, as well as the western and northern Eurasians. The Deng exhibited haplogroups O, D, N, and C, similar to most Sino‐Tibetan populations in the east. Short tandem repeat (STR) diversity within the dominant haplogroup O3 in Sino‐Tibetan populations showed that the Luoba are genetically cl... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5446385 Wed, 23 Nov 2011 05:00:00 +0100 5446385 http://www.medworm.com/index.php?rid=5415514&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00683.x SummaryIt has been shown that parametric analysis of linkage disequilibrium conditional on linkage using an overly deterministic model can be optimal for family‐based association analysis. However, if one applies this strategy carelessly, there is a risk of false inference. We analyse properties of such likelihood ratio tests when the assumed disease mode of inheritance is inaccurate. Under some conditions, problems result if one is not careful to consider what null hypothesis is being tested. We show that: (a) tests for which the null hypothesis assumes the absence of both linkage and association are independent of the true mode of inheritance; (b) likelihood ratio tests assuming either linkage or association under the null hypothesis may depend on the true mode of inheritance, leading ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5415514 Mon, 14 Nov 2011 05:00:00 +0100 5415514 http://www.medworm.com/index.php?rid=5499888&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00692.x This study demonstrates that TRMOOB, which is RFOOB plus MARS, has combined the strengths of RF and MARS in identifying SNP‐SNP interactions in a scenario of 100 candidate SNPs. TRMOOB had greater true positive rate and lower false positive rate compared with MARS, particularly for searching interactions with a strong association with the outcome. Therefore, the use of TRMOOB is favored for exploring SNP‐SNP interactions in a large‐scale genetic variation study. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5499888 Tue, 01 Nov 2011 04:00:00 +0100 5499888 http://www.medworm.com/index.php?rid=5453080&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00688.x SummaryVariants in the UGT1A1 gene and its promoter are known to determine levels of unconjugated bilirubin (UCB), but do not explain all cases of unconjugated hyperbilirubinemia. To discover associations with variants in genes other than UGT1A1, we undertook a genome‐wide association study. We recruited 200 participants to cover the entire range of quantitative variation in UCB level. The data set – after data curation, including analyses for population stratification and cryptic relatedness – comprised genotypes at 512,349 SNP loci on 182 individuals. Quantitative trait locus (QTL) association analyses were performed, after adjusting the UCB level for effects of age, gender, and genotype at the dinucleotide (TA) insertion locus in UGT1A1 that is known to significantly modul... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5453080 Tue, 01 Nov 2011 04:00:00 +0100 5453080 http://www.medworm.com/index.php?rid=5446384&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00689.x SummaryIdentifying population stratification and genotyping error are important for candidate gene association studies using the Transmission Disequilibrium Test (TDT). Although the TDT retains the prespecified Type I error in the presence of population stratification, the test may have decreased power in the presence of population stratification. Genotyping error can also cause the TDT to have an elevated Type I error. Differentiating population stratification from genotyping error remains a challenge for geneticists. Both genotyping error and population stratification can result in an increase in the observed homozygosity of a sample relative to that expected assuming Hardy‐Weinberg Equilibrium (HWE). We show that when family data are available, even if a limited number of markers are ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5446384 Tue, 01 Nov 2011 04:00:00 +0100 5446384 http://www.medworm.com/index.php?rid=5426953&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00685.x SummaryA large number of linkage and association studies of complex diseases focus on analysis of a more common or more easily measured disease endophenotype. The motivation for this approach is that there is a pleiotropic locus common to both the disease and the endophenotype and that this locus is a major genetic determinant of the endophenotype. In this paper, we determine the conditions under which the risk of the endophenotype in siblings of affected probands with disease equals the risk of the endophenotype in the offspring (parents) of affected parents (offspring) with disease. In doing so we prove that this equality holds if and only if the penetrance of either the endophenotype or the disease (but not necessarily both) is additive. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5426953 Tue, 01 Nov 2011 04:00:00 +0100 5426953 http://www.medworm.com/index.php?rid=5415513&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00686.x SummaryThe association between obesity and the fat mass and obesity‐associated (FTO) gene has been widely replicated among Caucasian populations. The limited number of studies assessing its significance in Asian populations has been somewhat conflicting. We performed a genetic association study of 51 tagging, genome‐wide association studies, and imputed single nucleotide polymorphisms with 12 measures of adiposity and skeletal robustness in two Samoan populations of Polynesia. We included 465 and 624 unrelated American Samoan and Samoan individuals, respectively; these populations derive from a single genetic background traced to Southeast Asia and represent one sociocultural unit, although they are economically disparate with distinct environmental exposures. American Samoans were sig... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5415513 Tue, 01 Nov 2011 04:00:00 +0100 5415513 http://www.medworm.com/index.php?rid=5372107&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00684.x In this study, we propose a novel Bayesian marker selection approach to perform a weighting‐based association test. In this approach, an individual association signal and its direction are used to weight variants. In addition, the predicted biological function of variants is taken as prior information to direct the selection of likely causal variants. Simulation studies show that the proposed method has improved power over several existing methods in certain conditions. Analyses of two empirical datasets demonstrate its applicability. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5372107 Tue, 01 Nov 2011 04:00:00 +0100 5372107 http://www.medworm.com/index.php?rid=5342082&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00682.x This study investigates associations of Lebanese mitochondrial DNA lineages with CAD and studies their correlation with other populations, exploring population structures that may infer mitochondria functional associations and reveal population movements and origins. Sequencing the mitochondrial hypervariable sequence 1 (HVS‐1) of 363 controls and 448 cases revealed that haplogroup W was more frequent (P= 0.013) in cases compared to controls, and was associated with increased risk of CAD (OR = 5.50, 95% CI = 1.50–35.30, P= 0.026) among Lebanese samples. Haplogroup A was only found in controls (P= 0.029). We have detected stronger geographic correlation between haplogroup W and CAD (Pearson's r= 0.316, P < 0.001) than between haplogroup A and CAD (r= 0.149, P < 0.001). HVS‐1 phy... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5342082 Sun, 23 Oct 2011 18:13:19 +0100 5342082 http://www.medworm.com/index.php?rid=5291422&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00681.x We present simulation studies to demonstrate the validity of the test and to evaluate its power. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5291422 Fri, 07 Oct 2011 02:18:56 +0100 5291422 http://www.medworm.com/index.php?rid=5291421&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00680.x SummaryIn population‐based household surveys, for example, the National Health and Nutrition Examination Survey (NHANES), blood‐related individuals are often sampled from the same household. Therefore, genetic data collected from national household surveys are often correlated due to two levels of clustering (correlation) with one induced by the multistage geographical cluster sampling, and the other induced by biological inheritance among multiple participants within the same sampled household. In this paper, we develop efficient statistical methods that consider the weighting effect induced by the differential selection probabilities in complex sample designs, as well as the clustering (correlation) effects described above. We examine and compare the magnitude of each level of cluste... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5291421 Fri, 07 Oct 2011 02:18:54 +0100 5291421 http://www.medworm.com/index.php?rid=5291420&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00677.x SummaryGenome‐wide association studies have transformed genetic studies of disease susceptibility, identifying many variants that may tag functional polymorphism nearby. Variants are often ascribed to a physically close gene exhibiting plausible functionality for a causal pathway. However, more physically remote genes may be at a lesser linkage or linkage disequilibrium (LD) distance from the tested SNP and could therefore contain the functional variant tagged. This analysis aims to identify instances where research may be misled by misassociation of a variant with a gene and develop tools to analyse genomic confounding. A catalogue of reported associations was systematically analysed for unreported genes which may represent the true functionality ascribed to a reported variant, calculat... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5291420 Fri, 07 Oct 2011 02:18:53 +0100 5291420 http://www.medworm.com/index.php?rid=5291419&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00678.x SummaryThe vast amount of recombination information in the human genome has long been ignored or deliberately avoided in studies on human population genetic relationships. One reason is that estimation of the recombination parameter from genotyping data is computationally challenging and practically difficult. Here we propose chromosome‐wide haplotype sharing (CHS) as a measure of genetic similarity between human populations, which is an indirect approach to integrate recombination information. We showed in both empirical and simulated data that recombination differences and genetic differences between human populations are strongly correlated, indicating that recombination events in different human populations are evolutionarily related. We further demonstrated that CHS can be used to r... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5291419 Fri, 07 Oct 2011 02:18:49 +0100 5291419 http://www.medworm.com/index.php?rid=5291418&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00676.x SummaryIn order to describe the isonymic structure of Paraguay, the distribution of 4,843,868 surnames of 2,882,163 persons was studied in the 18 departments and 237 districts of the nation. The correlations between isonymic and geographic distances for departments were r = 0.713 ± 0.052 for Euclidean distance, 0.597 ± 0.074 for Nei's and 0.582 ± 0.076 for Lasker's, and for districts r = 0.320 ± 0.007, 0.235 ± 0.009 and 0.422 ± 0.008, respectively. Average α was 151 for the entire country, 140.6 ± 6.5 for departments and 108.2 ± 2.7 for districts. The geographical distribution of districts’α is compatible with the settlement of subsequent groups of migrants moving from South towards the Centre and North of Paraguay. The geographical analysis of the first three components of Las... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5291418 Fri, 07 Oct 2011 02:18:46 +0100 5291418 http://www.medworm.com/index.php?rid=5244688&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00675.x SummaryPure subtelomeric deletion of the long arm of chromosome 6 is rare. The frequency of this deletion accounts for approximately 0.05% of subjects with intellectual disability and developmental delay with or without dysmorphic features. Common phenotypes associated with this deletion include intellectual disability, developmental delay, dysmorphic features, seizure, hypotonia, microcephaly and hypoplasia of the corpus callosum. The smallest overlapped region is approximately 0.4 Mb, and contains three known genes. Of these genes, TBP has been considered as a plausible candidate gene for the phenotype in patients with a subtelomeric 6q deletion. Analysis of the breakpoints in 14 cases revealed a potential common breakpoint interval 8.0–9.0 Mb from the chromosome 6q terminus where the ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5244688 Thu, 22 Sep 2011 04:00:00 +0100 5244688 http://www.medworm.com/index.php?rid=5216613&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00672.x SummaryHLA class I diversity (loci A, B and C) was analysed in four populations, two from North Cameroon (Podokwo and Uldeme) and two from South Cameroon (Ewondo and Bamileke). Northern and southern Cameroon populations show a substantial genetic diversity in terms of haplotype sharing and genetic distances, even despite the low percentage of variance due to differences among populations evidenced by analysis of molecular variance. The signals of differentiation among populations are consistent with their linguistic affiliation, and support previous evidence, based on autosomal microsatellites and protein loci, which has shown that the complex pattern of genetic variation of Cameroon can in part be described by contrasting the northern and southern part of the country. Looking at our resul... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5216613 Tue, 13 Sep 2011 04:00:00 +0100 5216613 http://www.medworm.com/index.php?rid=5216614&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00671.x SummaryHereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease frequently leading to dialysis, is associated with germline mutations of the CFH, CD46, or CFI genes. After identification of the mutation in an affected aHUS patient, single‐site gene testing of relatives is the preventive care perspective. However, clinical data for family counselling are scarce.From the German‐Speaking‐Countries‐aHUS‐Registry, 33 index patients with mutations were approached for permission to offer relatives screening for their family‐specific mutations and to obtain demographic and clinical data. Mutation screening was performed using direct sequencing. Age‐adjusted penetrance of aHUS was calculated for each gene in index cases and in mutation‐positive relatives.Sixty‐one ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5216614 Mon, 12 Sep 2011 04:00:00 +0100 5216614 http://www.medworm.com/index.php?rid=5244687&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00679.x SummaryAn archive of congenital human diseases is presented, aiming to contain all those where recessive (biallelic) can be compared with X‐linked and/or dominant (monoallelic) inheritance. A significant deficit of recessive inheritance is evident, both in disease inheritance and in contribution to inheritance per known disease gene. The deficit contrasts with expectation derived from the cell biology of mutation, and from the importance of recessive mutation in evolution and its preponderance in N‐ethyl‐N‐nitrosourea (ENU) mutagenesis. The deficit fits well with the standard model of demographic change since the neolithic era, and may also reflect natural selection acting on heterozygotes. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5244687 Thu, 01 Sep 2011 04:00:00 +0100 5244687 http://www.medworm.com/index.php?rid=5216612&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00674.x In conclusion, we have confirmed the strong association between FTO and obesity, and shown that only AA homozygotes are predisposed to develop obesity while TT homozygotes might be protected. Finally, we found no association between rs9939609 and a number of obesity‐related abnormalities. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5216612 Thu, 01 Sep 2011 04:00:00 +0100 5216612 http://www.medworm.com/index.php?rid=5202096&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00673.x SummaryThe linkage disequilibrium structure of the human genome allows identification of small sets of single nucleotide polymorphisms (SNPs) (tSNPs) that efficiently represent dense sets of markers. This structure can be translated into linear algebraic terms as evidenced by the well documented principal components analysis (PCA)‐based methods. Here we apply, for the first time, PCA‐based methodology for efficient genomewide tSNP selection; and explore the linear algebraic structure of the human genome. Our algorithm divides the genome into contiguous nonoverlapping windows of high linear structure. Coupling this novel window definition with a PCA‐based tSNP selection method, we analyze 2.5 million SNPs from the HapMap phase 2 dataset. We show that 10–25% of these SNPs suffice to ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5202096 Thu, 01 Sep 2011 04:00:00 +0100 5202096 http://www.medworm.com/index.php?rid=5189729&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00670.x SummaryRheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen (HLA) genomic region, most notably with a group of HLA‐DRB1 alleles termed the shared epitope (SE). There is also substantial evidence of other risk loci in the HLA region, but refinement has been hampered by extensive linkage disequilibrium (LD). Using genotype imputation, we analysed 6575 RA cases and controls with genotypes at 6180 HLA SNPs; about half the subjects had four‐digit DRB1 genotypes. Single‐SNP tests revealed hundreds of strong associations across the HLA region, even after adjusting for DRB1. We implemented penalised logistic regression in a multi‐SNP association analysis using the double‐exponential (DE) penalty term on the regression coefficients and the normal‐exponential... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5189729 Wed, 31 Aug 2011 23:00:00 +0100 5189729 http://www.medworm.com/index.php?rid=5123652&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00669.x SummaryAnimal studies have shown that the peroxime proliferator‐activated receptor delta (PPARD) gene regulates glucose metabolism and insulin sensitivity. Genetic variation in the PPARD gene might affect physical endurance and has been associated with obesity. We investigated the independent and modifying effect of variants in the PPARD gene with exercise participation and body mass index (BMI) on type 2 diabetes (T2D), using data from a genome‐wide association study (GWAS) of middle‐aged women living in Shanghai, China, with 1019 T2D cases and 1709 controls. The genotyping was performed using the Affymetrix Genome‐Wide Human SNP Array 6.0 platform. Imputation was used to determine missing genotypes. Participation in exercise was assessed by a questionnaire. Anthropometric variabl... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5123652 Sat, 13 Aug 2011 05:32:58 +0100 5123652 http://www.medworm.com/index.php?rid=5123651&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00668.x The objective of the study was to determine the association of the IRS1 (rs1801278), CAPN10 (rs3792267), TCF7L2 (rs7903146 and rs12255372), and PPARG (rs1801282) gene polymorphisms with T2D, in two different Mexican populations. We conducted a case‐control replication study in the state of Guerrero and in Mexico City, with 400 subjects from Guerrero and 1065 from Mexico City. Data were analyzed by logistic regression, adjusting by ancestry, age, gender, and BMI, to determine the association with T2D. Heterozygosity for the Gly972Arg variant of the IRS1 gene showed the strongest association for T2D in both analyzed samples (OR = 2.43, 95% CI 1.12–5.26 and 2.64, 95% CI 1.37–5.10, respectively). In addition, an association of two SNPs of the TCF7L2 gene with T2D was observed in both cit... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5123651 Sat, 13 Aug 2011 05:32:56 +0100 5123651 http://www.medworm.com/index.php?rid=5123650&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00666.x SummaryThe role of the lipoprotein‐associated phospholipase A2 gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single‐nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age‐matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high‐density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146–3.224]; P= 0.013). There was no ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5123650 Sat, 13 Aug 2011 05:32:55 +0100 5123650 http://www.medworm.com/index.php?rid=5123649&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00667.x SummaryWe performed a genome‐wide linkage analysis to identify susceptibility loci in a large six‐generation extended family previously reported with early‐onset osteoarthritis (OA) DNA sequencing was performed to investigate involvement of the COMP (Cartilage oligomeric matrix protein) gene in this family. The region covering D19S884, D19S226, and D19S414 on chromosome 19p following genome‐wide scan from 70 individuals of this kindred showed significant linkage, with a maximum point LOD (logarithm of the odds ratio) score of 2.51 at D19S226. Direct sequencing of the COMP gene, the most plausible candidate gene in the region, identified a c.2152C>T substitution in exon 18 which resulted in a substitution of tryptophan for arginine at position 718 located in the C terminal globul... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5123649 Sat, 13 Aug 2011 05:32:52 +0100 5123649 http://www.medworm.com/index.php?rid=5056599&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00664.x SummaryIn order to identify novel genetic variants that influence plasma lipid concentrations, we performed a genome‐wide association study (GWAS) comprised of 411 children under 18 years of age, ascertained at St. Jude Children's Research Hospital, all of whom were of European, African, or Mexican descent. Promising associations (p < 10−5) were subsequently examined in 1040 additional youths and 3508 adults from the Third National Health and Nutrition Examination Survey (NHANES III), a diverse population‐based study. Three genotype–phenotype associations replicated in NHANES III youths and three associated in NHANES III adults at p < 0.05; however, no single association was significant in both youths and adults. The most significant association (p= 0.009) in NHANES III youth... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5056599 Wed, 20 Jul 2011 23:00:00 +0100 5056599 http://www.medworm.com/index.php?rid=5046530&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00661.x In conclusion, we confirmed that circulating OPG is a heritable trait and there is a significant difference in heritability between sexes. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5046530 Sun, 17 Jul 2011 23:00:00 +0100 5046530 http://www.medworm.com/index.php?rid=5067513&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00662.x SummarySurfactant protein‐D (SP‐D) is expressed on mucosal surfaces and functions in the innate immune response to microorganisms. We studied the genetic association of the two nonsynonymous SP‐D single nucleotide polymorphisms (SNPs) rs721917 and rs2243639 in 256 inflammatory bowel disease (IBD) cases (123 CD and 133 UC) and 376 unrelated healthy individuals from an IBD population from Central Pennsylvania. Case‐control analysis revealed a significant association of rs2243639 with susceptibility to Crohn's disease (CD) (p= 0.0036), but not ulcerative colitis (UC) (p= 0.883), and no association of rs721917 with CD (p= 0.328) or UC (p= 0.218). Using intestinal tissues from 19 individuals heterozygous for each SNP, we compared allelic expression of these two SNPs between diseased and... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5067513 Thu, 30 Jun 2011 23:00:00 +0100 5067513 http://www.medworm.com/index.php?rid=5056598&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00665.x In conclusion, this study replicates and strengthens the evidence for association between polymorphisms of COL1A1 and TGFB1 in the genetic aetiology of otosclerosis. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5056598 Thu, 30 Jun 2011 23:00:00 +0100 5056598 http://www.medworm.com/index.php?rid=5046529&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00663.x In this study, we performed a mitochondria‐wide association study for osteoporosis in a large sample of 2286 unrelated Caucasian subjects. A total of 445 mtSNPs were genotyped and 72 mtSNPs survived the quality control. We first examined association between mtSNPs and bone mineral density (BMD), and identified that an mtSNP, mt4823 within the ND2 gene, was strongly associated with hip BMD (P= 2.05 × 10−4), even after Bonferroni correction. The C allele of mt4823 was associated with reduced hip BMD and the effect size (β) was ∼0.044. Another SNP mt15885 within the MT‐CYB gene was associated both with spine (P= 1.66 × 10−3) and hip BMD (P= 0.023). The T allele of mt15885 had a protective effect on spine (β= 0.064) and hip BMD (β= 0.038). Next, we classified subjects into the n... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=5046529 Thu, 30 Jun 2011 23:00:00 +0100 5046529 http://www.medworm.com/index.php?rid=4930454&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00659.x SummaryThere is a need for interdisciplinary assessments and interpretations of ‐omics underpinnings of human complex diseases. However, often investigators from different, yet overlapping, disciplines experience difficulties in understanding the other discipline's language and there is a clear need for establishing a platform that nourishes interdisciplinary team processes and allows tearing down the professional's tower of Babel. To accommodate these needs, the biennial mini‐conference Capita Selecta in Complex Disease Analysis was instigated. Abstracts are freely available online [http://www.aimontefiore.org/cscda2010/]. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930454 Thu, 16 Jun 2011 16:54:11 +0100 4930454 http://www.medworm.com/index.php?rid=4930453&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00656.x SummaryAn individual's genotypes at a group of single‐nucleotide polymorphisms (SNPs) can be used to predict that individual's ethnicity or ancestry. In medical studies, knowledge of a subject's ancestry can minimize possible confounding, and in forensic applications, such knowledge can help direct investigations. Our goal is to select a small subset of SNPs, from the millions already identified in the human genome, that can predict ancestry with a minimal error rate. The general form for this variable selection procedure is to estimate the expected error rates for sets of SNPs using a training dataset and consider those sets with the lowest error rates given their size. The quality of the estimate for the error rate determines the quality of the resulting SNPs. As the apparent error rat... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930453 Thu, 16 Jun 2011 16:54:10 +0100 4930453 http://www.medworm.com/index.php?rid=4930452&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00658.x SummarySuccessful aging (SA) is a multidimensional phenotype involving preservation of cognitive ability, physical function, and social engagement throughout life. Multiple components of SA are heritable, supporting a genetic component. The Amish are genetically and socially isolated with homogeneous lifestyles, making them a suitable population for studying the genetics of SA. DNA and measures of SA were collected on 214 cognitively intact Amish individuals over age 80. Individuals were grouped into a 13‐generation pedigree using the Anabaptist Genealogy Database. A linkage screen of 5944 single nucleotide polymorphisms (SNPs) was performed using 12 informative subpedigrees with an affected‐only 2‐point and multipoint linkage analysis. Eleven SNPs produced 2‐point LOD scores >2... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930452 Thu, 16 Jun 2011 16:54:09 +0100 4930452 http://www.medworm.com/index.php?rid=4930451&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00657.x SummaryTo test for and characterize heterogeneity in ancestral contributions to individuals among a population of Mexican American (MA) and non‐Hispanic white (NHW) stroke/transient ischemic attack (TIA) cases, data from a community‐based stroke surveillance study in south Texas were used. Strokes/TIA cases were identified (2004–2006) with a random sample asked to provide blood. Race‐ethnicity was self‐reported. Thirty‐three ancestry informative markers were genotyped and individual genetic admixture estimated using maximum likelihood methods. Three hypotheses were tested for each MA using likelihood ratio tests: (1) H0: μi = 0 (100% Native American), (2) H0: μi = 1.00 (100% European), (3) H0: μi = 0.59 (average European). Among 154 self‐identified MAs, estimated European ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930451 Thu, 16 Jun 2011 16:54:08 +0100 4930451 http://www.medworm.com/index.php?rid=4930450&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00660.x SummaryWhen pathogenic variants are rare then even among cases the proportion of subjects possessing a variant might be low, meaning that very large samples might be required to conclusively demonstrate evidence of an effect. Relatives of subjects within a case‐control sample might provide useful additional information.The method of model‐free linkage analysis implemented in MFLINK was adapted to incorporate linkage disequilibrium (LD) parameters in order to test for an effect of a putative pathogenic variant in complete LD with a disease locus. The effect of adding in to the analysis relatives of cases and controls found to carry the variant was investigated.When affected siblings or cousins of cases possessing the variant were incorporated they had a large effect on the results obtai... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4930450 Thu, 16 Jun 2011 16:54:04 +0100 4930450 http://www.medworm.com/index.php?rid=4838089&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00655.x SummaryWe studied 706 participants of the San Antonio Family Diabetes Study (SAFDS) and 586 male samples from the San Antonio Center for Biomarkers of Risk of Prostate Cancer (SABOR) and used 64 ancestry informative markers to compare admixture proportions between both groups. Existence of population substructure was demonstrated by the excess association of unlinked markers. In the SAFDS sample, ancestral proportions were estimated at 50.2 ± 0.6% European, 46.4 ± 0.6% Native American, and 3.1 ± 0.2% West African. For the SABOR sample, the proportions were 58.9 ± 0.7%, 38.2 ± 0.7%, and 2.9 ± 0.2%, respectively. Additionally, in the SAFDS subjects a highly significant negative correlation was found between individual Native American ancestry and skin reflectance (R2= 0.07, P= 0.00006)... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4838089 Tue, 17 May 2011 23:00:00 +0100 4838089 http://www.medworm.com/index.php?rid=4838088&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00651.x SummaryA variant allele, ADH1B*48His, also known as ADH1B*2, at the human Alcohol Dehydrogenase 1B gene (ADH1B) is strongly associated with alcoholism in some populations and has an unusual geographic distribution. Strong evidence implies selection has increased the frequency of this allele in some East Asian populations but does not fully explain its geographic pattern. We have studied haplotypes of 10 single nucleotide polymorphisms (SNPs) and two short tandem repeat polymorphisms (STRPs) in the ADH1B region in 2,206 individuals from a worldwide set of populations. These SNPs and STRPs define nine common haplogroups most of which have distinct geographic patterns. The haplogroups H5 and H6, both with the derived ADH1B*48His allele, appear restricted to the Middle East and East Asia, resp... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4838088 Sat, 30 Apr 2011 23:00:00 +0100 4838088 http://www.medworm.com/index.php?rid=4766940&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00654.x SummaryWe have used the gene‐centric Illumina HumanCVD BeadChip to identify common genetic determinants of Von Willebrand factor (vWF) levels in healthy men and women.The Whitehall II (WHII) study (n= 5592) and the British Women's Heart and Health Study (BWHHS) (n= 3445) were genotyped using the HumanCVD BeadChip. Replication was conducted in the British Regional Heart Study (n= 3897) and 1958 Birth Cohort (n= 5048).We identified 48 single nucleotide polymorphisms (SNPs) in four genes/regions associated with vWF at P < 10−4. These included 19 SNPs at the ABO blood group locus with the lead variant being rs657152 (P= 9.7 × 10−233). The lead variant in the 24 VWF SNPs was rs1063856 (P= 2.3 × 10−20). SNPs at ESR1 (rs6909023) and NRG1(rs1685103) showed modest associations with vWF... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4766940 Sat, 30 Apr 2011 09:47:40 +0100 4766940 http://www.medworm.com/index.php?rid=4766942&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00652.x SummaryThe spectrum of mutations in the von Willebrand factor (VWF) gene in a Swedish type 1 von Willebrand disease (VWD) population was investigated. To gain more knowledge about the dynamics of VWD mutations, the data were analyzed from a population genetics perspective. The VWF gene was resequenced in 54 Swedish patients diagnosed with type 1 VWD. Fifty‐five variable sites were located in exons, 10 in the promoter and 38 in introns. The spectrum of mutations was similar to a European study, but included 10 new candidate mutations. The synonymous sites were evenly distributed along the coding sequence, whereas nonsynonymous sites were located into three clusters. Overall, 44% of patients had no mutations or candidate mutations and no promoter haplotype was significantly associated with... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4766942 Wed, 27 Apr 2011 23:00:00 +0100 4766942 http://www.medworm.com/index.php?rid=4766941&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00653.x Summaryα thalassemia is the result of the loss of one or both copies of the two human α globin genes. α thalassemia appears to be the most common monogenic disease in the world and is in high frequency where malaria is, or has been, endemic. In nonmalarial environments, α thalassemia is rare and its frequency can be explained by a balance of deletional mutation and purifying selection. In malarial environments, the loss of one or two copies of the four α globin genes in normal diploid genotypes confers resistance (lower mortality) to malaria. Fitness estimates from data from Kenyan and Papua New Guinea populations are used to predict the increase in the −α haplotype (with one deleted gene). The frequency of double deletions (−− haplotypes) is higher in some Asian populations th... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4766941 Wed, 27 Apr 2011 23:00:00 +0100 4766941 http://www.medworm.com/index.php?rid=4708206&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00644.x SummaryWe narrowed chromosome 15q21–23 linkage to plasma high‐density lipoprotein cholesterol (HDL‐C) levels in Turkish families by fine mapping, then focused on glucuronic acid epimerase (GLCE), a heparan sulfate proteoglycan (HSPG) biosynthesis enzyme. HSPGs participate in lipid metabolism along with apolipoprotein (apo) E. Of 31 SNPs in the GLCE locus, nine analyzed by haplotype were associated with HDL‐C and triglyceride levels (permuted p = 0.006 and 0.013, respectively) in families. Of five tagging GLCE SNPs in two cohorts of unrelated subjects, three (rs16952868, rs11631403, and rs3865014) were associated with triglyceride and HDL‐C levels in males (nonpermuted p < 0.05). The association was stronger in APOE 2/3 subjects (apoE2 has reduced binding to HSPGs) and reached ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4708206 Thu, 14 Apr 2011 03:20:56 +0100 4708206 http://www.medworm.com/index.php?rid=4708205&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00643.x SummaryParkinson disease (PD) is a common complex neurodegenerative disorder with an underlying genetic etiology that has been difficult to dissect. Although some PD risk genes have been discovered, most of the underlying genetic etiology remains unknown. To further elucidate the genetic component, we have undertaken a genome‐wide linkage screen in an isolated founder population of Amish living in the Midwestern United States. We performed tests for linkage and for association using a marker set of nearly 6000 single‐nucleotide polymorphisms. Parametric multipoint linkage analysis generated a logarithm of the odds of linkage (LOD) score of 2.44 on chromosome 6 in the SYNE1 gene, approximately 8 Mbp from the PARK2 gene. In a different region on chromosome 6 (∼67 Mbp from PARK2) an ass... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4708205 Thu, 14 Apr 2011 03:20:53 +0100 4708205 http://www.medworm.com/index.php?rid=4708204&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00645.x SummaryFrom its inception in 1925 through the almost 30 years that it carried the title of Annals of Eugenics, this journal published numerous articles on the statistical aspects of genetic linkage analysis and its applications to family pedigree data. This overview discusses 40 papers on linkage analysis published in the Annals. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4708204 Thu, 14 Apr 2011 03:20:52 +0100 4708204 http://www.medworm.com/index.php?rid=4708203&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00611.x SummaryThis journal began in 1925 as the Annals of Eugenics. Much has changed since then. The original Editors’ primary eugenic objective was not achieved, and eugenics justifiably became notorious for racism and gross abuse of human rights. But one founding aim was to publish advances in statistical genetics, and that objective prospered in the journal's pages from its beginning to the present day. The online availability of the original issues will be useful to those interested in the history of both eugenics and human genetics and will provide a reminder of how the careless use of genetical concepts can go astray. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4708203 Thu, 14 Apr 2011 03:20:51 +0100 4708203 http://www.medworm.com/index.php?rid=4708202&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00648.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4708202 Thu, 14 Apr 2011 03:20:51 +0100 4708202 http://www.medworm.com/index.php?rid=4708201&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00649.x SummaryEugenics in most western countries in the first four decades of the 20th century was based on the idea that genes control most human phenotypic traits, everything from physical features such as polydactyly and eye colour to physiological conditions such as the A‐B‐O blood groups to mental and personality traits such as “feeblemindedness,” alcoholism and pauperism. In assessing the development of the eugenics movement—its rise and decline between 1900 and 1950—it is important to recognise that its naïve assumptions and often flawed methodologies were openly criticised at the time by scientists and nonscientists alike. This paper will present a brief overview of the critiques launched against eugenicists’ claims, particularly criticisms of the American school led by Cha... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4708201 Thu, 14 Apr 2011 03:20:50 +0100 4708201 http://www.medworm.com/index.php?rid=4708200&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00650.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4708200 Thu, 14 Apr 2011 03:20:49 +0100 4708200 http://www.medworm.com/index.php?rid=4675215&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00646.x SummaryRecent genome‐wide single nucleotide polymorphism (SNP) association studies (GWAS) have identified a number of SNPs that were significantly associated with coronary artery disease and myocardial infarction (MI). However, many independent replication studies in other populations are needed to unequivocally confirm the GWAS association. To assess GWAS association, we have established a case‐control cohort consisting of 1231 well‐characterised MI patients and 560 controls without detectable coronary stenosis, all selected from the Cleveland Genebank population. The Genebank cohort has sufficient power to detect the association between MI and four GWAS SNPs, including rs17465637 within the MIA3 gene, rs2943634 (intergenic), rs6922269 in MTHFD1L, and rs599839 near SORT1. SNPs were ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4675215 Sun, 03 Apr 2011 23:00:00 +0100 4675215 http://www.medworm.com/index.php?rid=4675214&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00647.x SummaryMutational inactivation of the VHL gene is the cause of von Hippel‐Lindau (VHL) disease, an autosomal dominant hereditary cancer syndrome predisposing to haemangioblastomas, pheochromocytomas and clear‐cell renal carcinomas. The gene product (pVHL) functions as an adapter in cellular processes including cell growth and apoptosis. VHL mutation analysis was carried out in 426 unrelated subjects with phenotypes ranging from VHL syndrome, to isolated VHL‐related tumours that could represent the first manifestation of the disease. A total of 111 individuals were found to carry alterations, with large deletions representing 40% of the variants. Eighteen of the 95 detected variants were novel, seemingly disease‐causing mutations; their pathogenic role has been evaluated in silico f... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4675214 Tue, 01 Mar 2011 00:00:00 +0100 4675214 http://www.medworm.com/index.php?rid=4630241&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00642.x SummaryThe prevalence of hypophosphatasia (HP), a rare metabolic disorder due to loss‐of‐function mutations in the ALPL gene, has never been estimated in the European population. Only one published study evaluated the incidence of severe HP at 1/100,000 in Canada 53 years ago. Moderate forms of hypophosphatasia (mHP), including HP with moderate bone features and the mildest form odontohypophosphatasia, reflect both recessive and dominant inheritance, and are therefore expected to be more frequent than severe forms of HP. Here we estimated both the prevalences of severe and mHP in European populations. The prevalence of severe HP was estimated at 1/300,000 on the basis of the number of cases tested in our laboratory and originating from France during the period 2000–2009. The prevalen... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4630241 Tue, 01 Mar 2011 00:00:00 +0100 4630241 http://www.medworm.com/index.php?rid=4589122&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00641.x SummaryWe undertook a candidate locus study of the HIN200 gene cluster on 1q21‐23 in UK systemic lupus erythematosus (SLE) families. To date, despite mounting evidence demonstrating the importance of these proteins in autoimmune disease, cancer, apoptosis, inflammation, and cell cycle arrest, there has been a dearth of data with respect to the genetic characterisation of the HIN200 locus in SLE or any other disease. We typed 83 single nucleotide polymorphisms (SNPs) across 317 kb of the HIN200 cluster in 428 UK SLE families and sought replication from a European‐American lupus cohort. We do not find strong evidence of SNP association in either cohort. Interestingly, we do observe a trend for association with certain HIN200 SNPs and serologic subphenotypes in UK SLE that parallels the a... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4589122 Tue, 01 Mar 2011 00:00:00 +0100 4589122 http://www.medworm.com/index.php?rid=4520950&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2011.00640.x SummaryIn the age of high‐density genome‐wide association (GWAS) data, correcting for multiple comparisons is a substantial issue for genetic epidemiological studies. However, the current manuscript review process generally requires both stringent correction and independent replication. The result of this stringency is that studies that are published suffer from inflated Type 2 error rates (false negatives), thereby removing many likely real signals from follow‐up. Elimination of these alleles, if they are truly associated, from further study will slow research progress in studies of complex disease. We argue that this method of correction is overly conservative, especially in an age when high‐density follow‐up experiments are possible and reasonably inexpensive. (Source: Annals ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4520950 Fri, 25 Feb 2011 23:03:39 +0100 4520950 http://www.medworm.com/index.php?rid=4481298&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00637.x SummaryAsthma manifests as TH2‐dominant airway inflammation regulated by inducible T‐cell kinase (ITK). To investigate associations between genetic variants of the ITK gene and asthma, 31 single‐nucleotide polymorphisms (SNPs) were genotyped in 303 normal controls and 498 asthmatics and the two groups were compared using logistic regression models. The functional effects of the ITK promoter SNP were assessed using pGL3 luciferase reporter systems and gel‐shift assays. The minor allele−196C>T in the promoter region of the ITK gene was significantly more frequent in asthmatics than in controls. The luciferase activity of the PGL3‐ITK‐196T allele construct was higher than that of the −196C allele. In the gel‐shift assay, −196T double‐stranded oligonucleotides bound mo... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4481298 Wed, 16 Feb 2011 05:22:36 +0100 4481298 http://www.medworm.com/index.php?rid=4481299&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00635.x SummarySingle nucleotide polymorphisms (SNPs) at the adiponectin and resistin loci are strongly associated with hypoadiponectinemia and hyperresistinemia, which may eventually increase risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease. Real‐time PCR was used to genotype SNPs of the adiponectin (SNP+45T>G, SNP+276G>T, SNP+639T>C, and SNP+1212A>G) and resistin (SNP‐420C>G and SNP+299G>A) genes in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40 and 70 years old. The genotyping results for each SNP marker was verified by sequencing. The anthropometric clinical and metabolic parameters of subjects were recorded. None of these SNPs at the adiponect... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4481299 Tue, 15 Feb 2011 00:00:00 +0100 4481299 http://www.medworm.com/index.php?rid=4463371&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00638.x SummaryVariation of a short (TA)n repeat sequence (rs8175347) covering the TATA box of UGT1A1 (UDP‐glucuronosyltransferase1A1) is associated with hyperbilirubinaemia (Gilbert's syndrome) and adverse drug reactions, and is used for dosage advice for irinotecan. Several reports indicate that the low‐activity (risk) alleles ((TA)7 and (TA)8)) are very frequent in Africans but the patterns of association with other variants in the UGT1A gene complex that may modulate these responses are not well known. rs8175347 and two other clinically relevant UGT1A variants (rs11692021 and rs10929302) were assayed in 2616 people from Europe and Africa. Low‐activity (TA)n alleles frequencies were highest in equatorial Africa, (TA)7, being the most common in Cameroon, Ghana, southern Sudan, and in Ethio... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4463371 Fri, 11 Feb 2011 23:13:41 +0100 4463371 http://www.medworm.com/index.php?rid=4359685&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00634.x SummaryCoronary heart disease (CHD) is a complex disease, which is influenced not only by genetic and environmental factors but also by gene–environment (GE) interactions in interconnected biological pathways or networks. The classical methods are inadequate for identifying GE interactions due to the complex relationships among risk factors, mediating risk factors (e.g., hypertension, blood lipids, and glucose), and CHD. Our aim was to develop a two‐level structural equation model (SEM) to identify genes and GE interactions in the progress of CHD to take into account the causal structure among mediating risk factors and CHD (Level 1), and hierarchical family structure (Level 2). The method was applied to the Framingham Heart Study (FHS) Offspring Cohort data. Our approach has several a... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4359685 Mon, 17 Jan 2011 00:00:00 +0100 4359685 http://www.medworm.com/index.php?rid=4422983&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00639.x SummaryPopulation stratification is an important issue in case–control studies of disease‐marker association. Failure to properly account for population structure can lead to spurious association or reduced power. In this article, we compare the performance of six methods correcting for population stratification in case–control association studies. These methods include genomic control (GC), EIGENSTRAT, principal component‐based logistic regression (PCA‐L), LAPSTRUCT, ROADTRIPS, and EMMAX. We also include the uncorrected Armitage test for comparison. In the simulation studies, we consider a wide range of population structure models for unrelated samples, including admixture. Our simulation results suggest that PCA‐L and LAPSTRUCT perform well over all the scenarios studied, whe... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4422983 Sat, 01 Jan 2011 00:00:00 +0100 4422983 http://www.medworm.com/index.php?rid=4359684&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00636.x SummaryA common design in family‐based association studies consists of siblings without parents. Several methods have been proposed for analysis of sibship data, but they mostly do not allow for missing data, such as haplotype phase or untyped markers. On the other hand, general methods for nuclear families with missing data are computationally intensive when applied to sibships, since every family has missing parents that could have many possible genotypes. We propose a computationally efficient model for sibships by conditioning on the sets of alleles transmitted into the sibship by each parent. This means that the likelihood can be written only in terms of transmitted alleles and we do not have to sum over all possible untransmitted alleles when they cannot be deduced from the sibling... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4359684 Sat, 01 Jan 2011 00:00:00 +0100 4359684 http://www.medworm.com/index.php?rid=4292117&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00633.x In this report, we present genetic etiology of 28 PWS patients from Taiwan. Consistent with the genetic etiology findings from Western populations, the type II deletion appears to be the most common deletion subtype. Furthermore, the ratio of the two most common deletion subtypes and the ratio of the maternal heterodisomy to isodisomy cases observed from this study are in agreement with previous findings from Western populations. In addition, we identified and further mapped the deletion breakpoints in two patients with atypical deletions using array CGH (comparative genomic hybridization). Despite the relatively small numbers of patients in each subgroup, our findings suggest that the genomic architecture responsible for the recurrent recombination in PWS is conserved in Taiwanese of the ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4292117 Wed, 29 Dec 2010 01:19:52 +0100 4292117 http://www.medworm.com/index.php?rid=4286890&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00632.x This study refined the 16p region contributing to vascular calcification. The causal variants remain to be identified, but results are consistent with a linkage peak that is due to multiple common variants, though rare variants cannot be excluded. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4286890 Fri, 24 Dec 2010 23:03:46 +0100 4286890 http://www.medworm.com/index.php?rid=4286891&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00631.x SummaryVitamin D and vitamin D receptor (VDR) have been postulated as environmental and genetic factors in neurodegeneration disorders including multiple sclerosis (MS), Alzheimer disease (AD), and recently Parkinson disease (PD). Given the sparse data on PD, we conducted a two‐stage study to evaluate the genetic effects of VDR in PD. In the discovery stage, 30 tagSNPs in VDR were tested for association with risk as a discrete trait and age‐at‐onset (AAO) as a quantitative trait in 770 Caucasian PD families. In the validation stage, 18 VDR SNPs were tested in an independent Caucasian cohort (267 cases and 267 controls) constructed from a genome‐wide association study (GWAS). In the discovery dataset, SNPs in the 5′ end of VDR were associated with both risk and AAO with more signi... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4286891 Fri, 24 Dec 2010 00:00:00 +0100 4286891 http://www.medworm.com/index.php?rid=4263036&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00630.x SummaryThe search for the missing heritability in genome‐wide association studies (GWAS) has become an important focus for the human genetics community. One suspected location of these genetic effects is in gene–gene interactions, or epistasis. The computational burden of exploring gene–gene interactions in the wealth of data generated in GWAS, along with small to moderate sample sizes, have led to epistasis being an afterthought, rather than a primary focus of GWAS analyses. In this review, I discuss some potential approaches to filter a GWAS dataset to a smaller, more manageable dataset where searching for epistasis is considerably more feasible. I describe a number of alternative approaches, but primarily focus on the use of prior biological knowledge from databases in the public ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4263036 Thu, 16 Dec 2010 13:51:09 +0100 4263036 http://www.medworm.com/index.php?rid=4263035&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00618.x SummaryGenome‐wide association studies (GWAS) are now clearly established as a powerful method for detecting loci involved in the etiology of common complex diseases. Most diseases and traits studied using the GWAS approach now have several loci that have been shown to be convincingly replicated. It is generally the case that these loci have been identified using single locus association scans of genotyped or imputed SNPs and very few loci have been identified by taking interactions into account. We propose a method that assesses the evidence of association at each SNP by modeling the effect of the locus in combination with other known loci. We use a Bayesian model averaging approach that combines the evidence across several different plausible models for the way in which the loci intera... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4263035 Thu, 16 Dec 2010 13:50:48 +0100 4263035 http://www.medworm.com/index.php?rid=4240660&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00628.x SummaryThe literature on epistasis describes various methods to detect epistatic interactions and to classify different types of epistasis. Reconstructability analysis (RA) has recently been used to detect epistasis in genomic data. This paper shows that RA offers a classification of types of epistasis at three levels of resolution (variable‐based models without loops, variable‐based models with loops, state‐based models). These types can be defined by the simplest RA structures that model the data without information loss; a more detailed classification can be defined by the information content of multiple candidate structures. The RA classification can be augmented with structures from related graphical modeling approaches. RA can analyze epistatic interactions involving an arbitra... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4240660 Mon, 06 Dec 2010 00:00:00 +0100 4240660 http://www.medworm.com/index.php?rid=4240659&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00629.x SummaryIn the presence of epistasis multilocus association tests of human complex traits can provide powerful methods to detect susceptibility variants. We undertook multilocus analyses in 1924 type 2 diabetes cases and 2938 controls from the Wellcome Trust Case Control Consortium (WTCCC). We performed a two‐dimensional genome‐wide association (GWA) scan using joint two‐locus tests of association including main and epistatic effects in 70,236 markers tagging common variants. We found two‐locus association at 79 SNP‐pairs at a Bonferroni‐corrected P‐value = 0.05 (uncorrected P‐value = 2.14 × 10−11). The 79 pair‐wise results always contained rs11196205 in TCF7L2 paired with 79 variants including confirmed variants in FTO, TSPAN8, and CDKAL1, which are associated in the a... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4240659 Mon, 06 Dec 2010 00:00:00 +0100 4240659 http://www.medworm.com/index.php?rid=4218230&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00622.x This study provides preliminary genetic evidence for the role of variant of SLCO1B1 in the susceptibility to human EH in Uyghurs. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4218230 Wed, 01 Dec 2010 00:00:00 +0100 4218230 http://www.medworm.com/index.php?rid=4218229&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00627.x SummaryComplex phenotypes are known to be associated with interactions among genetic factors. A growing body of evidence suggests that gene–gene interactions contribute to many common human diseases. Identifying potential interactions of multiple polymorphisms thus may be important to understand the biology and biochemical processes of the disease etiology. However, despite the great success of genome‐wide association studies that mostly focus on single locus analysis, it is challenging to detect these interactions, especially when the marginal effects of the susceptible loci are weak and/or they involve several genetic factors. Here we describe a Bayesian classification tree model to detect such interactions in case‐control association studies. We show that this method has the poten... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4218229 Wed, 01 Dec 2010 00:00:00 +0100 4218229 http://www.medworm.com/index.php?rid=4218233&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00623.x SummaryEnsemble methods (such as Bagging and Random Forests) take advantage of unstable base learners (such as decision trees) to improve predictions, and offer measures of variable importance useful for variable selection. LogicFS has been proposed as such an ensemble learner for case‐control studies when interactions of single nucleotide polymorphisms (SNPs) are of particular interest. LogicFS uses bootstrap samples of the data and employs the Boolean trees derived in logic regression as base learners to create ensembles of models that allow for the quantification of the contributions of epistatic interactions to the disease risk. In this article, we propose an extension of logicFS suitable for case‐parent trio data, and derive an additional importance measure that is much less influ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4218233 Tue, 30 Nov 2010 00:00:00 +0100 4218233 http://www.medworm.com/index.php?rid=4218232&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00618.x SummaryGenome‐wide association studies (GWAS) are now clearly established as a powerful method for detecting loci involved in the etiology of common complex diseases. Most diseases and traits studied using the GWAS approach now have several loci that have been shown to be convincingly replicated. It is generally the case that these loci have been identified using single locus association scans of genotyped or imputed SNPs and very few loci have been identified by taking interactions into account. We propose a method that assesses the evidence of association at each SNP by modeling the effect of the locus in combination with other known loci. We use a Bayesian model averaging approach that combines the evidence across several different plausible models for the way in which the loci intera... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4218232 Tue, 30 Nov 2010 00:00:00 +0100 4218232 http://www.medworm.com/index.php?rid=4218231&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00625.x SummaryWell‐established examples of genetic epistasis between a pair of loci typically show characteristic patterns of phenotypic distributions in joint genotype tables. However, inferring epistasis given such data is difficult due to the lack of power in commonly used approaches, which decompose the epistatic patterns into main plus interaction effects followed by testing the interaction term. Testing additive‐only or all terms may have more power, but they are sensitive to nonepistatic patterns. Alternatively, the epistatic patterns of interest can be enumerated and the best matching one is found by searching through the possibilities. Although this approach requires multiple testing correction over possible patterns, each pattern can be fitted with a regression model with just one d... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4218231 Tue, 30 Nov 2010 00:00:00 +0100 4218231 http://www.medworm.com/index.php?rid=4202249&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00626.x We present a one‐sample permutation test for testing transmission disequilibrium hypotheses in triad studies, and show how this test can be used for multiple single nucleotide polymorphism (SNP) testing. The resulting multiple comparison procedure is shown in the case of the transmission disequilibrium test to control the familywise error. Furthermore, this procedure can handle multiple possible modes of risk inheritance per SNP. The resulting permutational procedure is shown through simulation of SNP data to be more powerful than the Bonferroni procedure when the SNPs are in linkage disequilibrium. Moreover, permutations implicitly avoid any multiple comparison correction penalties when the SNP has a rare allele. The method is illustrated by analyzing a large candidate gene study of neu... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4202249 Thu, 25 Nov 2010 00:00:00 +0100 4202249 http://www.medworm.com/index.php?rid=4188750&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00619.x SummaryLinkage detection of a trait involves detecting regions of the genome that influence the trait. A wide variety of statistical models are currently employed for linkage analysis of quantitative traits. Many of these models are developed under some assumptions of the trait distributions. Violation of the assumptions about the trait generally affects the type I error and power for linkage detection. In this paper, we have proposed a trait‐model‐free approach for linkage analysis of a quantitative trait in general pedigrees. The conditional segregation of marker alleles given the trait is modeled using a latent‐variable logistic model. A likelihood‐ratio test is used to test for linkage under our model. The main applicability of this approach lies in the fact that it always prov... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4188750 Mon, 22 Nov 2010 00:00:00 +0100 4188750 http://www.medworm.com/index.php?rid=4188749&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00620.x This study examines the reciprocal effects of cultural evolution, and population dynamics in pre‐Columbian southern Peru by the analysis of DNA from pre‐Columbian populations that lived in the fringe area between the Andean highlands and the Pacific coast. The main objective is to reveal whether the transition from the Middle Horizon (MH: 650–1000 AD) to the Late Intermediate Period (LIP: 1000–1400 AD) was accompanied or influenced by population dynamic processes. Tooth samples from 90 individuals from several archaeological sites, dating to the MH and LIP, in the research area were collected to analyse mitochodrial, and Y‐chromosomal genetic markers. Coding region polymorphisms were successfully analysed and replicated for 72 individuals, as were control region sequences for 65 ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4188749 Mon, 22 Nov 2010 00:00:00 +0100 4188749 http://www.medworm.com/index.php?rid=4148696&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00616.x SummaryIn the investigation of disease aetiology, the genome‐wide association study (GWAS) provides a hypothesis‐free investigation of the broader human genome and, as with all scientific investigations, replication is essential to validate any findings. To date, six GWAS have been performed to investigate the influence of common genetic variation in Parkinson's disease (PD) and only two associations have been replicated: alpha synuclein (SNCA) and microtubule‐associated protein tau (MAPT), both PD candidate genes before GWAS. In our population‐based study, we genotyped four of the top single‐nucleotide polymorphisms (SNPs) from a previous study. By using the identical analytic method and genetic model in our independent sample, we provide evidence for replication of rs1724425 ne... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4148696 Mon, 08 Nov 2010 00:00:00 +0100 4148696 http://www.medworm.com/index.php?rid=4195371&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00624.x SummaryA central goal of human genetics is to identify susceptibility genes for common human diseases. An important challenge is modelling gene–gene interaction or epistasis that can result in nonadditivity of genetic effects. The multifactor dimensionality reduction (MDR) method was developed as a machine learning alternative to parametric logistic regression for detecting interactions in the absence of significant marginal effects. The goal of MDR is to reduce the dimensionality inherent in modelling combinations of polymorphisms using a computational approach called constructive induction. Here, we propose a Robust Multifactor Dimensionality Reduction (RMDR) method that performs constructive induction using a Fisher's Exact Test rather than a predetermined threshold. The advantage of ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4195371 Mon, 01 Nov 2010 00:00:00 +0100 4195371 http://www.medworm.com/index.php?rid=4188748&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00621.x SummaryCurrent disease association studies are routinely conducted on a genome‐wide scale, testing hundreds of thousands or millions of genetic markers. Besides detecting marginal associations of individual markers with the disease, it is also of interest to identify gene–gene and gene–environment interactions, which confer susceptibility to the disease risk. The astronomical number of possible combinations of markers and environmental factors, however, makes interaction mapping a daunting task both computationally and statistically. In this paper, we review and discuss a set of Bayesian partition methods developed recently for mapping single‐nucleotide polymorphisms in case‐control studies, their extension to quantitative traits, and further generalization to multiple traits. We... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4188748 Mon, 01 Nov 2010 00:00:00 +0100 4188748 http://www.medworm.com/index.php?rid=4148695&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00617.x SummaryData from uniparentally inherited genetic systems were used to trace evolution of human populations. Reconstruction of the past primarily relies on variation in present‐day populations, limiting historical inference to lineages that are found among living subjects. Our analysis of four population groups in the Gaspé Peninsula, demonstrates how this may occasionally lead to erroneous interpretations. Mitochondrial DNA analysis of Gaspesians revealed an important admixture with Native Americans. The most likely scenario links this admixture to French‐Canadians from the St. Lawrence Valley who moved to Gaspesia in the 19th century. However, in contrast to genetic data, analysis of genealogical record shows that Native American maternal lineages were brought to Gaspesia in the 18th... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4148695 Mon, 01 Nov 2010 00:00:00 +0100 4148695 http://www.medworm.com/index.php?rid=4115206&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00615.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4115206 Fri, 29 Oct 2010 23:34:29 +0100 4115206 http://www.medworm.com/index.php?rid=4076379&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00610.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4076379 Mon, 18 Oct 2010 13:54:40 +0100 4076379 http://www.medworm.com/index.php?rid=4071765&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00609.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4071765 Sat, 16 Oct 2010 14:29:27 +0100 4071765 http://www.medworm.com/index.php?rid=4071764&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00614.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4071764 Sat, 16 Oct 2010 14:29:25 +0100 4071764 http://www.medworm.com/index.php?rid=4071763&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00613.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4071763 Sat, 16 Oct 2010 14:29:24 +0100 4071763 http://www.medworm.com/index.php?rid=4039285&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00612.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4039285 Tue, 31 Aug 2010 23:00:00 +0100 4039285 http://www.medworm.com/index.php?rid=4021500&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00608.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=4021500 Tue, 31 Aug 2010 23:00:00 +0100 4021500 http://www.medworm.com/index.php?rid=3991708&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00603.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3991708 Tue, 31 Aug 2010 23:00:00 +0100 3991708 http://www.medworm.com/index.php?rid=3975465&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00607.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3975465 Tue, 31 Aug 2010 23:00:00 +0100 3975465 http://www.medworm.com/index.php?rid=3971983&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00605.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3971983 Tue, 31 Aug 2010 23:00:00 +0100 3971983 http://www.medworm.com/index.php?rid=3971982&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00606.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3971982 Tue, 31 Aug 2010 23:00:00 +0100 3971982 http://www.medworm.com/index.php?rid=3941217&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00604.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3941217 Tue, 31 Aug 2010 23:00:00 +0100 3941217 http://www.medworm.com/index.php?rid=3884211&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00601.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3884211 Fri, 20 Aug 2010 08:37:09 +0100 3884211 http://www.medworm.com/index.php?rid=3884212&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00600.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3884212 Sat, 31 Jul 2010 23:00:00 +0100 3884212 http://www.medworm.com/index.php?rid=3779467&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00599.x The objective is a fuller understanding of the bias in transmission rates and what is driving it. Extending previously published findings, we derive parental mating-type probabilities in cases and use them to obtain transmission rates, which we then compare to G×E. Through simulation, we investigate the practical implications of the bias for a transmission-based test of G×E. We find that general population characteristics distort the picture of G×E obtained from transmission rates: the stratum-specific mating-type probabilities under G [minus] E dependence and the allele frequency under independence. Furthermore, the transmission-based test has inflated error rates relative to a likelihood-based test. Our investigation provides further insight into how and why transmission-based tests a... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3779467 Thu, 22 Jul 2010 23:00:00 +0100 3779467 http://www.medworm.com/index.php?rid=3779468&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00593.x Haplotypes are an important concept for genetic association studies, but involve uncertainty due to statistical reconstruction from single nucleotide polymorphism (SNP) genotypes and genotype error. We developed a re-sampling approach to quantify haplotype misclassification probabilities and implemented the MC-SIMEX approach to tackle this as a 3 × 3 misclassification problem. Using a previously published approach as a benchmark for comparison, we evaluated the performance of our approach by simulations and exemplified it on real data from 15 SNPs of the APM1 gene. Misclassification due to reconstruction error was small for most, but notable for some, especially rarer haplotypes. Genotype error added misclassification to all haplotypes resulting in a non-negligible drop in sensitivity. In... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3779468 Wed, 21 Jul 2010 23:00:00 +0100 3779468 http://www.medworm.com/index.php?rid=3775401&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00598.x When estimating the power of genetic association studies, the allele and genotype frequencies are often assumed to be known, and the numbers of individuals with each genotype are set equal to their expectations under Hardy-Weinberg equilibrium. In fact, both allele and genotype frequencies are unknown and thus random. It has previously been suggested that ignoring uncertainty in these parameters could lead to inflated power expectations. To overcome the problem, one can average power estimates over the distributions of unknown frequencies. We investigate the power-averaging method and find that, despite the intuitive appeal, it may not improve accuracy in practice, while significantly increasing computational time. For a fixed allele frequency, we show that the amount of overestimation dim... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3775401 Tue, 20 Jul 2010 23:00:00 +0100 3775401 http://www.medworm.com/index.php?rid=3775400&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00590.x Allelic variants of a single nucleotide polymorphism (SNP), rs7566605, located approximately 10 kb upstream of the INSIG2 gene have been found in association with body weight and with other clinical features related to obesity in some populations but not in others. Our objective was to test the association of this SNP in obese children and adolescents from the genetically isolated population of Sardinia. We tested the association of rs7566605 with body mass index (BMI) and with serum glucose and insulin concentrations and a surrogate measure of insulin resistance (HOMA-IR) in a cohort of 747 Sardinian obese children and adolescents. A case control analysis was performed using 548 ethnically-matched healthy controls. Allelic frequencies of the SNP were similar between patients and controls.... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3775400 Tue, 20 Jul 2010 23:00:00 +0100 3775400 http://www.medworm.com/index.php?rid=3760640&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00594.x In this paper, we propose a two-stage approach based on 17 biologically plausible models to search for two-locus combinations that have significant joint effects on the disease status in genome-wide association (GWA) studies. In the two-stage analyses, we only test two-locus joint effects of SNPs that show modest marginal effects. We use simulation studies to compare the power of our two-stage analysis with a single-marker analysis and a two-stage analysis by using a full model. We find that for most plausible interaction effects, our two-stage analysis can dramatically increase the power to identify two-locus joint effects compared to a single-marker analysis and a two-stage analysis based on the full model. We also compare two-stage methods with one-stage methods. Our simulation results ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3760640 Fri, 16 Jul 2010 23:00:00 +0100 3760640 http://www.medworm.com/index.php?rid=3752933&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00596.x Appetite regulatory neural network and adipocyte homeostasis molecular pathways are critical to long-term weight maintenance. Associations between obesity-related phenotypes and four genes in these pathways [ndash] leptin (LEP), leptin receptor (LEPR), neuropeptide Y2 receptor (NPY2R) and peptide YY (PYY) were examined in CARDIA Study participants (aged 18[ndash]30 at recruitment in 1985[ndash]6). Weight, BMI and waist circumference were measured at baseline and at years 2, 5, 7, 10, 15, and 20. Genotyping was conducted using tag SNPs characterising common genetic variations in these genes. Generalized estimating equation (GEE) models estimated associations between SNPs and repeated anthropometric measurements, controlling for sex and age. False discovery rate was used to adjust for multip... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3752933 Wed, 14 Jul 2010 23:00:00 +0100 3752933 http://www.medworm.com/index.php?rid=3752935&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00595.x Otosclerosis is a common form of conductive hearing loss, caused by an abnormal bone remodelling in the otic capsule. Both environmental and genetic factors have been implicated in the etiology of this disease. A recent genome wide association study identified two regions associated with otosclerosis, one on chr7q22.1, located in the RELN gene, and one on chr11q13.1. A second study in four European populations has replicated the association of the RELN gene with otosclerosis. To investigate the association of these loci with otosclerosis in a non-European population, we tested 11 SNPs from the two regions in 149 unrelated Tunisian patients and 152 controls. Four SNPs were significantly associated with otosclerosis. Three SNPs are located in the RELN region and the last one is located in th... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3752935 Tue, 13 Jul 2010 23:00:00 +0100 3752935 http://www.medworm.com/index.php?rid=3752934&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00597.x Unraveling the genetic background of common complex traits is a major goal in modern genetics. In recent years, genome-wide association (GWA) studies have been conducted with large-scale data sets of genetic variants. Most of those studies have relied on single-marker approaches that identify single genetic factors individually and can be limited in considering fully the joint effects of multiple genetic factors on complex traits. Joint identification of multiple genetic factors would be more powerful and would provide better prediction on complex traits since it utilizes combined information across variants. Here we propose a multi-stage approach for GWA analysis: (1) prescreening, (2) joint identification of putative SNPs based on elastic-net variable selection, and (3) empirical replica... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3752934 Tue, 13 Jul 2010 23:00:00 +0100 3752934 http://www.medworm.com/index.php?rid=3860879&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00602.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3860879 Wed, 30 Jun 2010 23:00:00 +0100 3860879 http://www.medworm.com/index.php?rid=3840693&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00579.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840693 Wed, 30 Jun 2010 23:00:00 +0100 3840693 http://www.medworm.com/index.php?rid=3840692&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00577.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840692 Wed, 30 Jun 2010 23:00:00 +0100 3840692 http://www.medworm.com/index.php?rid=3840691&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00580.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840691 Wed, 30 Jun 2010 23:00:00 +0100 3840691 http://www.medworm.com/index.php?rid=3840690&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00588.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840690 Wed, 30 Jun 2010 23:00:00 +0100 3840690 http://www.medworm.com/index.php?rid=3840689&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00585.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840689 Wed, 30 Jun 2010 23:00:00 +0100 3840689 http://www.medworm.com/index.php?rid=3840688&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00586.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840688 Wed, 30 Jun 2010 23:00:00 +0100 3840688 http://www.medworm.com/index.php?rid=3840687&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00584.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840687 Wed, 30 Jun 2010 23:00:00 +0100 3840687 http://www.medworm.com/index.php?rid=3840686&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00582.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840686 Wed, 30 Jun 2010 23:00:00 +0100 3840686 http://www.medworm.com/index.php?rid=3840685&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00589.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840685 Wed, 30 Jun 2010 23:00:00 +0100 3840685 http://www.medworm.com/index.php?rid=3840684&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00581.x Summary (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840684 Wed, 30 Jun 2010 23:00:00 +0100 3840684 http://www.medworm.com/index.php?rid=3840682&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00595.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840682 Wed, 30 Jun 2010 23:00:00 +0100 3840682 http://www.medworm.com/index.php?rid=3840681&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00597.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840681 Wed, 30 Jun 2010 23:00:00 +0100 3840681 http://www.medworm.com/index.php?rid=3840680&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00594.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840680 Wed, 30 Jun 2010 23:00:00 +0100 3840680 http://www.medworm.com/index.php?rid=3840679&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00599.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840679 Wed, 30 Jun 2010 23:00:00 +0100 3840679 http://www.medworm.com/index.php?rid=3675410&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00592.x The study of disease etiology and the search for susceptible genes of schizophrenia have attracted scientists' attention for decades. Many findings however are inconsistent, possibly due to the higher order interactions involving multi-dimensional genetic and environmental factors or due to the commingling of different ethnic groups. Several studies applied generalized linear mixed models (GLMMs) with family data to identify the genetic contribution to, and environmental influence on, schizophrenia, and to clarify the existence and sources of familial aggregation. Based on an extended Bayesian model averaging (EBMA) procedure, here we estimate the gene-gene (GG) and gene-environment (GE) interactions, and heritability of schizophrenia via variance components of random-effects in GLMMs. Our... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3675410 Fri, 18 Jun 2010 23:00:00 +0100 3675410 http://www.medworm.com/index.php?rid=3675411&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00591.x Developments in quantitative PCR technologies have greatly improved our ability to detect large genome rearrangements. In particular oligonucleotide-based array comparative genomic hybridisation has become a useful tool for appropriate and rapid detection of breakpoints. In this work, we have analysed 80 samples (42 unknown CF alleles) applying three quantitative technologies (MLPA, qPCR and array-CGH) to detect recurrent as well as novel large rearrangements in the Spanish CF population. Three deletions and one duplication have been identified in five alleles (12%). Interestingly, we provide the comprehensive characterisation of the first duplication in our CF cohort. The new CFTRdupProm-3 mutation spans 35.7 kb involving the 5'-end of the CFTR gene. Additionally, the RNA analysis has rev... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3675411 Wed, 16 Jun 2010 23:00:00 +0100 3675411 http://www.medworm.com/index.php?rid=3664891&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00587.x The standard in genetic association studies of complex diseases is replication and validation of positive results, with an emphasis on assessing the predictive value of associations. In response to this need, a number of analytical approaches have been developed to identify predictive models that account for complex genetic etiologies. Multifactor Dimensionality Reduction (MDR) is a commonly used, highly successful method designed to evaluate potential gene-gene interactions. MDR relies on classification error in a cross-validation framework to rank and evaluate potentially predictive models. Previous work has demonstrated the high power of MDR, but has not considered the accuracy and variance of the MDR prediction error estimate. Currently, we evaluate the bias and variance of the MDR err... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3664891 Tue, 15 Jun 2010 23:00:00 +0100 3664891 http://www.medworm.com/index.php?rid=3617131&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00588.x Population-based genetic association analysis may suffer from the failure to control for confounders such as population stratification (PS). There has been extensive study on the influence of PS on candidate gene-disease association analysis, but much less attention has been paid to its influence on marker-disease association analysis. In this paper, we focus on the Pearson [chi]2 test and the trend test for marker-disease association analysis. The mean and variance of the test statistics are derived under presence of PS, so that the power and inflated type I error rate can be evaluated. It is shown that the bias and the variance distortion are not zero in the presence of both PS and penetrance heterogeneity (PH). Unlike candidate gene-disease association analysis, when PS is present, the ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3617131 Mon, 31 May 2010 23:00:00 +0100 3617131 http://www.medworm.com/index.php?rid=3598320&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00583.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3598320 Tue, 25 May 2010 23:00:00 +0100 3598320 http://www.medworm.com/index.php?rid=3504305&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00578.x Emerging evidence indicates that the DRD1-BDNF-DRD3 cluster plays an important role in nicotine addiction. We have performed an association analysis of 42 SNPs within these genes with cigarette consumption in a group of 341 schizophrenia patients. The ACCG haplotype consisting of four BDNF markers (Val66Met (rs6265), rs11030104, rs2049045 and rs7103411) showed an association with the risk of smoking (p = 0.0002). Both DRD1 markers tested (rs4532 and rs686) and the DRD3 marker (rs1025398) showed association with quantity of tobacco smoked (p = 0.01, 0.005 and 0.002, respectively). Our findings are preliminary; however, they support the involvement of the DRD1, BDNF and DRD3 genes in smoking behaviour. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3504305 Sun, 25 Apr 2010 23:00:00 +0100 3504305 http://www.medworm.com/index.php?rid=3504306&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00577.x Central congenital hypoventilation syndrome (CCHS) is an autonomous control disease producing hypoventilation, high PaCO2, and low PaO2 during quiet sleep. The main gene variants detected in CCHS are mutations in the PHOX2b gene in up to 97% of isolated cases. However, CCHS is sometimes associated with autonomic diseases such as Hirschsprung disease (HSCR). Since genomic rearrangements in particularly sensitive areas of the RET protooncogene and/or associated genes may account for the CCHS/HSCR phenotype in patients without other detectable RET variants, the aim of the present study was to identify rearrangements in the coding sequence of RET as well as in three HSCR-associated genes (ZEB2, EDN3 and GDNF) in CCHS/HSCR patients by using Multiplex Ligation-dependent Probe Amplification (MLPA... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3504306 Sat, 24 Apr 2010 23:00:00 +0100 3504306 http://www.medworm.com/index.php?rid=3442718&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00572.x We describe an alternative to the permutation approach in testing for interaction, a parametric bootstrap approach. Using simulations, we compare the finite-sample properties of a few often-used permutation tests and the parametric bootstrap. We consider interactions of an exposure with single and multiple polymorphisms. Finally, we address when permutation tests of interaction will be approximately valid in large samples for specific test statistics. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3442718 Tue, 06 Apr 2010 23:00:00 +0100 3442718 http://www.medworm.com/index.php?rid=3840683&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00572.x (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3840683 Wed, 31 Mar 2010 23:00:00 +0100 3840683 http://www.medworm.com/index.php?rid=3423677&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00568.x Imprinting is critical to understanding disease expression. It can be detected using linkage information, but the effects of potential confounders (heterogeneity, sex-specific penetrance, and sex-biased ascertainment) have not been explored. We examine power and confounders in two imprinting detection approaches, and we explore imprinting-linkage interaction. One method (PP) models imprinting by maximising lod scores w.r.t. parent-specific penetrances. The second (DRF) approximates imprinting by maximising lods over differential male-female recombination fractions. We compared power, type 1 error, and confounder effects in these two methods, using computer-simulated data. We varied heterogeneity, penetrance, family and dataset size, and confounders that might mimic imprinting. Without hete... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3423677 Tue, 30 Mar 2010 23:00:00 +0100 3423677 http://www.medworm.com/index.php?rid=3423676&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00569.x Friedreich's ataxia (FRDA) is caused by expansion of GAA repeats in the frataxin (FXN) gene on chromosome 9q13-q21.1. We analysed the origin of FRDA in 21 North Indian (NI) and eight South Indian (SI) families using five single nucleotide polymorphisms (SNPs) and a microsatellite marker spanning the GAA repeats. The NI and SI families were derived from Indo-European and Dravidian linguistic backgrounds respectively. The frequency of large normal (LNs) alleles of the GAA repeat correlate with the overall lower prevalence of FRDA in India compared to the European population. All of the expanded alleles in the Indian population share a common core haplotype suggesting a founder effect. The expanded alleles in the NI population demonstrate more similarity to those of Europeans in terms of age ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3423676 Tue, 30 Mar 2010 23:00:00 +0100 3423676 http://www.medworm.com/index.php?rid=3423675&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00570.x Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P= 0.035). A significant interaction with smoking was detected at rs2248814 (P= 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3423675 Tue, 30 Mar 2010 23:00:00 +0100 3423675 http://www.medworm.com/index.php?rid=3353238&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00562.x We examined the association of 166 single nucleotide polymorphisms (SNPs) in cytokines and cytokine related genes with cytokine concentrations (IL-1[beta], IL-8, and IL-10) in the amniotic fluid (AF). These cytokines have been associated with spontaneous preterm birth (PTB) and their genetic regulation may play a role in disease risk. These associations were studied in both PTB and term births in African Americans and Caucasians; maternal and fetal genotypes were studied separately. Analyses modeled genotype, pregnancy status, and marker by pregnancy status (case/control) interaction with cytokine concentration as outcome. Our results indicate that AF cytokines (IL-1[beta] and IL-10) were associated with interactions between pregnancy status and both maternal and fetal SNPs, with the most ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3353238 Wed, 10 Mar 2010 00:00:00 +0100 3353238 http://www.medworm.com/index.php?rid=3353237&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00567.x Crohn's disease (CD), a type of chronic inflammatory bowel disease (IBD), is commonly found in European and East Asian countries. The calculated heritability of CD appears to be higher than that of ulcerative colitis (UC), another type of IBD. Recent genome-wide association studies (GWAS) have identified more than thirty CD-associated genes/regions in the European population. In the East Asian population, however, a clear association between CD and an associated gene has only been detected with TNFSF15. In order to determine if CD susceptibility differs geographically, nine SNPs from seven of the European CD-associated genomic regions were selected for analysis. The genotype frequencies for these SNPs were compared among the 380 collected Japanese samples, which consisted of 212 IBD cases ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3353237 Wed, 10 Mar 2010 00:00:00 +0100 3353237 http://www.medworm.com/index.php?rid=3321249&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00566.x Rare mutations in more than 20 genes have been suggested to cause dilated cardiomyopathy (DCM), but explain only a small percentage of cases, mainly in familial forms. We hypothesised that more common variants may also play a role in increasing genetic susceptibility to DCM, similar to that observed in other common complex disorders. To test this hypothesis, we performed case-control analyses on all DNA polymorphic variation identified in a resequencing study of six candidate DCM genes (CSRP3, LDB3, MYH7, SCN5A, TCAP, and TNNT2) conducted in 289 unrelated white probands with DCM of unknown cause and 188 unrelated white controls. In univariate analyses, we identified associated common variants at LDB3 site 10779, LDB3 site 57877, MYH7 sites 16384 and 17404, and TCAP sites 140 and 1735. Mult... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3321249 Tue, 02 Mar 2010 00:00:00 +0100 3321249 http://www.medworm.com/index.php?rid=3321251&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00561.x Heart failure is a leading cause of death of people in South Asia, and cardiomyopathy is a major cause of heart failure. Myosin binding protein C (MYBPC3) is expressed in the heart muscle, where it regulates the cardiac response to adrenergic stimulation and is important for the structural integrity of the sarcomere. Mutations in the MYBPC3 gene are associated with hypertrophic or dilated cardiomyopathies. A 25-base-pair deletion in intron 32 causes skipping of the downstream exon and is associated with familial cardiomyopathy. To date, this deletion is found primarily in India and South Asia, although it is also found at low frequency in Southeast Asia. In order to better characterise the distribution of this variant, we determined its frequency in 447 individuals from 19 populations, inc... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3321251 Mon, 01 Mar 2010 00:00:00 +0100 3321251 http://www.medworm.com/index.php?rid=3321250&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00565.x The purpose of this study was to estimate the heritability of obesity-related phenotypes and investigate the association of adiponectin gene polymorphisms +45T>G and +276G>T with these measures in Chinese twins. 1260 twin pairs were recruited from two cities through the Chinese National Twin Registry System from 2001 to 2005. Two SNPs at the adiponectin locus (+45T>G and +276G>T) were genotyped. Structural equation modeling (SEM) was used to estimate heritability and the best-fitting variance component model. The regular association among all twins was analysed with generalised estimating equations (GEE). Sib-transmission/disequilibrium test (TDT) within dizygotic (DZ) twin pairs discordant for their genotype was performed using SEM. Additive genetic, common and unique environmental (ACE) ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3321250 Mon, 01 Mar 2010 00:00:00 +0100 3321250 http://www.medworm.com/index.php?rid=3317681&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2010.00564.x We screened the GJB2 gene for mutations in 534 (108 multiplex and 426 simplex) probands with non-syndromic sensorineural deafness, who were ascertained through the only residential school for the deaf in Mongolia, and in 217 hearing controls. Twenty different alleles, including four novel changes, were identified. Biallelic GJB2 mutations were found in 4.5% of the deaf probands (8.3% in multiplex, 3.5% in simplex). The most common mutations were c.IVS1 + 1G > A (c.-3201G > A) and c.235delC with allele frequencies of 3.5% and 1.5%, respectively. The c.IVS1 + 1G > A mutation appears to have diverse origins based on associated multiple haplotypes. The p.V27I and p.E114G variants were frequently detected in both deaf probands and hearing controls. The p.E114G variant was always in cis with the... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3317681 Mon, 01 Mar 2010 00:00:00 +0100 3317681 http://www.medworm.com/index.php?rid=3166173&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00558.x In this study, we investigated 20 asthma candidate genes from this region for all possible informative polymorphisms within our population, linkage disequilibrium (LD) structure and tagging SNP transferability from HapMap populations. We re-sequenced these genes and identified 267 polymorphisms including 26 insertion-deletions, four microsatellite markers and 237 single nucleotide polymorphisms. The region contained 17 distinct LD blocks with the largest within the serine peptidase inhibitor kazal type 5 (SPINK5) gene spanning 23 kb. Of the 267 polymorphisms identified, 40% are represented in HapMap Han Chinese from Beijing and 29% in Han Chinese from Denver. 72% of the polymorphisms can be represented by tagged SNPs from the HapMap Beijing Han Chinese population and are highly correlated ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3166173 Wed, 13 Jan 2010 00:00:00 +0100 3166173 http://www.medworm.com/index.php?rid=3166172&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00559.x A rare mutation in the RSPH9 gene leading to primary ciliary dyskinesia was previously identified in two Bedouin families, one from Israel and one from the United Arab Emirates (UAE). Herein we analyse mutation segregation in the Israeli family, present the clinical disease spectrum, and estimate mutation age in the two families. Mutation segregation was studied by restriction fragment length analysis. Mutation ages were estimated using a model of the decrease in the length of ancestral haplotypes. The mutations in each of the two families had a common ancestor less than 95 and less than 17 generations in the past. If the mutations in the two families are descended from a common ancestor, that mutation would have to have arisen at least 150 generations ago. If the Bedouin population has be... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3166172 Wed, 13 Jan 2010 00:00:00 +0100 3166172 http://www.medworm.com/index.php?rid=3166171&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00560.x This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3166171 Wed, 13 Jan 2010 00:00:00 +0100 3166171 http://www.medworm.com/index.php?rid=3091700&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00551.x The inflammatory cytokine interleukin-6 (IL-6) is a main regulator of fibrinogen synthesis, though its interaction with fibrinogen genes (FGA, FGB, FGG) and subsequent impact on cardiovascular disease (CVD) risk is not well-studied. We investigated joint associations of fibrinogen and IL6 tagSNPs with fibrinogen concentrations, carotid intima-media thickness, and myocardial infarction or ischemic stroke in 3900 European-American Cardiovascular Health Study participants. To identify combinations of genetic main effects and interactions associated with outcomes, we used logic regression. We also evaluated whether the relationship between fibrinogen SNPs and fibrinogen level varied by IL-6 level using linear regression models with multiplicative interaction terms. Combinations of fibrinogen a... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3091700 Wed, 16 Dec 2009 15:31:25 +0100 3091700 http://www.medworm.com/index.php?rid=3091704&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00556.x We investigated the bio-geographic ancestry of Argentineans, and quantified their genetic admixture, analyzing 246 unrelated male individuals from eight provinces of three Argentinean regions using ancestry-sensitive DNA markers (ASDM) from autosomal, Y and mitochondrial chromosomes. Our results demonstrate that European, Native American and African ancestry components were detectable in the contemporary Argentineans, the amounts depending on the genetic system applied, exhibiting large inter-individual heterogeneity. Argentineans carried a large fraction of European genetic heritage in their Y-chromosomal (94.1%) and autosomal (78.5%) DNA, but their mitochondrial gene pool is mostly of Native American ancestry (53.7%); instead, African heritage was small in all three genetic systems ( (So... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3091704 Tue, 15 Dec 2009 00:00:00 +0100 3091704 http://www.medworm.com/index.php?rid=3091703&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00549.x The Pro11Leu substitution in the AGXT gene, which causes primary hyperoxaluria type 1, is found with high frequency in some human populations (e.g., 5[ndash]20% in Caucasians). It has been suggested that this detrimental mutation could have been positively selected in populations with a meat-rich diet. In order to test this hypothesis, we investigated the occurrence of Pro11Leu in both herder and agriculturalist populations from Central Asia. We found a lower frequency of this detrimental mutation in herders, whose diet is more meat-rich, as compared to agriculturalists, which therefore challenges the universality of the previous claim. Furthermore, when combining our original data with previously published results, we could show that the worldwide genetic differentiation measured at the P... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3091703 Tue, 15 Dec 2009 00:00:00 +0100 3091703 http://www.medworm.com/index.php?rid=3091702&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00557.x In conclusion, our data suggest, although do not prove, different evolutionary histories in the F7 promoter region between Mediterraneans and Amerindians. (Source: Annals of Human Genetics) Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3091702 Tue, 15 Dec 2009 00:00:00 +0100 3091702 http://www.medworm.com/index.php?rid=3091701&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00554.x Atypical hemolytic uremic syndrome (aHUS) is caused by several susceptibility genes. A registry including analyses of susceptibility genes, familial occurrence and genotype-phenotype correlation should provide classification insights. Registry data of 187 unrelated index patients included age at onset, gender, family history, relapse of aHUS and potentially triggering conditions. Mutation analyses were performed in the genes CFH, CD46 and CFI and in the six potential susceptibility genes, FHR1 to FHR5 and C4BP. Germline mutations were identified in 17% of the index cases; 12% in CFH, 3% in CD46 and 2% in CFI. Twenty-nine patients had heterozygous mutations and one each had a homozygous and compound heterozygous mutation. Mutations were not found in the genes FHR1-5 and C4BP. In 40% of the ... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3091701 Tue, 15 Dec 2009 00:00:00 +0100 3091701 http://www.medworm.com/index.php?rid=3014626&cid=s_33043_50_f&fid=33043&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1469-1809.2009.00555.x Recent genome-wide association studies have identified a novel polymorphism, rs1042725, in the HMGA2 gene for human adult height, a highly heritable complex trait. Replications in independent populations are needed to evaluate a positive finding and determine its generality. Thus, we performed a replication study to examine the associations between polymorphisms in HMGA2 and adult height in two US Caucasian populations (an unrelated sample of 998 subjects and a family-based sample of 8385 subjects) and a Chinese population (1638 unrelated Han subjects). We confirmed the association between rs1042725 in HMGA2 and adult height both in the unrelated and family-based Caucasian populations (overall P= 4.25 × 10[minus]9). Another two SNPs (rs7968902 and rs7968682), which were in high linkage di... Annals of Human Genetics journals http://www.medworm.com/rss/comments.php?id=3014626 Sat, 21 Nov 2009 00:00:00 +0100 3014626