Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

PLoS Genet 2014 Aug 7;10(8):e1004517. Epub 2014 Aug 7.

Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. 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. 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. 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. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. 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. 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)

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http://dx.doi.org/10.1371/journal.pgen.1004517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125087PMC
August 2014
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