#Dr iftikar kullo free

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Received: JanuAccepted: JPublished: August 7, 2014 PLoS Genet 10(8):Įditor: Eleftheria Zeggini, Wellcome Trust Sanger Institute, United Kingdom (2014) Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes. Our results highlight the importance of performing genetic studies in non-European populations to fine map the causal genetic variants.Ĭitation: Ng MCY, Shriner D, Chen BH, Li J, Chen W-M, Guo X, et al. While 56% of these loci were shared between African Americans and the other populations, the strongest associations in African Americans are often found in nearby single nucleotide polymorphisms (SNPs) instead of the original SNPs reported in other populations due to differential genetic architecture across populations. We also examined 158 loci previously reported to be associated with T2D or regulating glucose homeostasis. Following replication in additional 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry, we identified two novel and three previous reported T2D loci reaching genome-wide significance. In this study, we performed meta-analysis of 17 GWAS in 8,284 cases and 15,543 controls to explore the genetic architecture of T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.ĭespite the higher prevalence of type 2 diabetes (T2D) in African Americans than in Europeans, recent genome-wide association studies (GWAS) were examined primarily in individuals of European ancestry. Overall, this study identified two novel susceptibility loci for T2D in African Americans. These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2×10 −23 < locus-wide P<0.05). We identified three known loci ( TCF7L2, HMGA2 and KCNQ1) and two novel loci ( HLA-B and INS-IGF2) at genome-wide significance (4.15×10 −94< P<5×10 −8, odds ratio (OR) = 1.09 to 1.36). Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans.

Dr iftikar kullo