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)
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.
Impact Factor
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Times Cited
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Cited By
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Susceptibility Loci; Transgenic Mice; Hla-b; Confirmation; Population; Haplotypes; Obesity; Risk; Expression; Efficient
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2014
Prepublished im Jahr
HGF-Berichtsjahr
2014
ISSN (print) / ISBN
1553-7390
e-ISSN
1553-7404
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 10,
Heft: 8,
Seiten: ,
Artikelnummer: e100451
Supplement: ,
Reihe
Verlag
Public Library of Science (PLoS)
Verlagsort
San Francisco
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30502 - Diabetes: Pathophysiology, Prevention and Therapy
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504100-001
G-521600-002
G-504091-002
G-504000-002
Förderungen
Copyright
Erfassungsdatum
2014-10-13