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

TitleMeta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.
Publication TypeJournal Article
Year of Publication2014
AuthorsC Y Ng M, Shriner D, Chen BH, Li J, Chen W-M, Guo X, Liu J, Bielinski SJ, Yanek LR, Nalls MA, Comeau ME, Rasmussen-Torvik LJ, Jensen RA, Evans DS, Sun YV, An P, Patel SR, Lu Y, Long J, Armstrong LL, Wagenknecht L, Yang L, Snively BM, Palmer ND, Mudgal P, Langefeld CD, Keene KL, Freedman BI, Mychaleckyj JC, Nayak U, Raffel LJ, Goodarzi MO, Chen Y-DIda, Taylor HA, Correa A, Sims M, Couper DJ, Pankow JS, Boerwinkle E, Adeyemo A, Doumatey A, Chen G, Mathias RA, Vaidya D, Singleton AB, Zonderman AB, Igo RP, Sedor JR, Kabagambe EK, Siscovick DS, McKnight B, Rice K, Liu Y, Hsueh W-C, Zhao W, Bielak LF, Kraja A, Province MA, Bottinger EP, Gottesman O, Cai Q, Zheng W, Blot WJ, Lowe WL, Pacheco JA, Crawford DC, Grundberg E, Rich SS, M Hayes G, Shu X-O, Loos RJF, Borecki IB, Peyser PA, Cummings SR, Psaty BM, Fornage M, Iyengar SK, Evans MK, Becker DM, Kao LWH, Wilson JG, Rotter JI, Sale MM, Liu S, Rotimi CN
Secondary AuthorsBowden DW
Corporate AuthorsFIND Consortium, eMERGE Consortium, DIAGRAM Consortium, MuTHER Consortium, MEta-analysis of type 2 DIabetes in African Americans Consortium
JournalPLoS Genet
Volume10
Issue8
Paginatione1004517
Date Published2014 Aug
ISSN1553-7404
KeywordsAfrican Americans, Diabetes Mellitus, Type 2, Genome-Wide Association Study, HLA-B27 Antigen, HMGA2 Protein, Humans, KCNQ1 Potassium Channel, Mutant Chimeric Proteins, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein
Abstract

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)

DOI10.1371/journal.pgen.1004517
Alternate JournalPLoS Genet
PubMed ID25102180
PubMed Central IDPMC4125087
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