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Ng, M.C.Y.* ; Shriner, D.* ; Chen, B.H.* ; Li, J.* ; Chen, W.* ; Guo, X.* ; Liu, J.* ; Bielinski, S.J.* ; Yanek, L.R.* ; Nalls, M.A.* ; Comeau, M.E.* ; Rasmussen-Torvik, L.J.* ; Jensen, R.A.* ; Evans, D.S.* ; Sun, Y.V.* ; An, P.* ; Patel, S.R.* ; Lu, Y.* ; Long, J.* ; Armstrong, L.L.* ; Wagenknecht, L.* ; Yang, L.* ; Snively, B.M.* ; Palmer, N.D.* ; Mudgal, P.* ; Langefeld, C.D.* ; Keene, K.L.* ; Freedman, B.I.* ; Mychaleckyj, J.C.* ; Nayak, U.* ; Raffel, L.J.* ; Goodarzi, M.O.* ; Chen, Y.I.* ; Taylor, H.A.* ; Correa, A.* ; Sims, M.* ; Couper, D.* ; Pankow, J.S.* ; Boerwinkle, E.* ; Adeyemo, A.* ; Doumatey, A.* ; Chen, G.* ; Mathias, R.A.* ; Vaidya, D.* ; Singleton, A.B.* ; Zonderman, A.B.* ; Igo, R.P.* ; Sedor, J.R.* ; FIND Consortium (*) ; Kabagambe, E.K.* ; Siscovick, D.S.* ; McKnight, B.* ; Rice, K.* ; Liu, Y.* ; Hsueh, W.C.* ; Zhao, W.* ; Bielak, L.F.* ; Kraja, A.* ; Province, M.A.* ; Bottinger, E.P.* ; Gottesman, O.* ; Cai, Q.* ; Zheng, W.* ; Blot, W.J.* ; Lowe, W.L.* ; Pacheco, J.A.* ; Crawford, D.C.* ; eMERGE Consortium (*) ; DIAGRAM Consortium (Gieger, C. ; Grallert, H. ; Illig, T. ; Klopp, N. ; Müller-Nurasyid, M. ; Peters, A.) ; Grundberg, E.* ; MuTHER Consortium (*) ; Rich, S.S.* ; Hayes, M.G.* ; Shu, X.* ; Loos, R.J.F.* ; Borecki, I.B.* ; Peyser, P.A.* ; Cummings, S.R.* ; Psaty, B.M.* ; Fornage, M.* ; Iyengar, S.K.* ; Evans, M.K.* ; Becker, D.M.* ; Kao, W.H.L.* ; Wilson, J.G.* ; Rotter, J.I.* ; Sale, M.M.* ; Liu, S.* ; Rotimi, C.N.* ; Bowden, D.W.* ; MEDIA Consortium (*)

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

PLoS Genet. 10:e100451 (2014)
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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 (4.15x10(-94) < P < 5x10(-8), odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2x10(-23) < locus-wide P<0.05). 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. Overall, this study identified two novel susceptibility loci for 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Susceptibility Loci; Transgenic Mice; Hla-b; Confirmation; Population; Haplotypes; Obesity; Risk; Expression; Efficient
Language english
Publication Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 10, Issue: 8, Pages: , Article Number: e100451 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place San Francisco
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
CCG Nutrigenomics and Type 2 Diabetes (KKG-KDN)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30502 - Diabetes: Pathophysiology, Prevention and Therapy
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-521600-002
G-504091-002
G-504000-002
DOI 10.1371/journal.pgen.1004517
WOS ID WOS:000341577800019
Erfassungsdatum 2014-10-13
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