Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
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Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. / Mahajan, Anubha; Go, Min Jin; Zhang, Weihua; Below, Jennifer E; Gaulton, Kyle J; Ferreira, Teresa; Horikoshi, Momoko; Johnson, Andrew D; Ng, Maggie C Y; Prokopenko, Inga; Saleheen, Danish; Wang, Xu; Zeggini, Eleftheria; Abecasis, Goncalo R; Adair, Linda S; Almgren, Peter; Atalay, Mustafa; Aung, Tin; Baldassarre, Damiano; Balkau, Beverley; Bao, Yuqian; Barnett, Anthony H; Barroso, Ines; Basit, Abdul; Been, Latonya F; Beilby, John; Bell, Graeme I; Benediktsson, Rafn; Bergman, Richard N; Boehm, Bernhard O; Boerwinkle, Eric; Bonnycastle, Lori L; Burtt, Noël; Cai, Qiuyin; Campbell, Harry; Carey, Jason; Cauchi, Stephane; Caulfield, Mark; Chan, Juliana C N; Chang, Li-Ching; Chang, Tien-Jyun; Chang, Yi-Cheng; Charpentier, Guillaume; Chen, Chien-Hsiun; Chen, Han; Chen, Yuan-Tsong; Chia, Kee-Seng; Chidambaram, Manickam; Chines, Peter S; Jonsson, Anna Elisabet; Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium.
In: Nature Genetics, Vol. 46, No. 3, 03.2014, p. 234-44.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
AU - Mahajan, Anubha
AU - Go, Min Jin
AU - Zhang, Weihua
AU - Below, Jennifer E
AU - Gaulton, Kyle J
AU - Ferreira, Teresa
AU - Horikoshi, Momoko
AU - Johnson, Andrew D
AU - Ng, Maggie C Y
AU - Prokopenko, Inga
AU - Saleheen, Danish
AU - Wang, Xu
AU - Zeggini, Eleftheria
AU - Abecasis, Goncalo R
AU - Adair, Linda S
AU - Almgren, Peter
AU - Atalay, Mustafa
AU - Aung, Tin
AU - Baldassarre, Damiano
AU - Balkau, Beverley
AU - Bao, Yuqian
AU - Barnett, Anthony H
AU - Barroso, Ines
AU - Basit, Abdul
AU - Been, Latonya F
AU - Beilby, John
AU - Bell, Graeme I
AU - Benediktsson, Rafn
AU - Bergman, Richard N
AU - Boehm, Bernhard O
AU - Boerwinkle, Eric
AU - Bonnycastle, Lori L
AU - Burtt, Noël
AU - Cai, Qiuyin
AU - Campbell, Harry
AU - Carey, Jason
AU - Cauchi, Stephane
AU - Caulfield, Mark
AU - Chan, Juliana C N
AU - Chang, Li-Ching
AU - Chang, Tien-Jyun
AU - Chang, Yi-Cheng
AU - Charpentier, Guillaume
AU - Chen, Chien-Hsiun
AU - Chen, Han
AU - Chen, Yuan-Tsong
AU - Chia, Kee-Seng
AU - Chidambaram, Manickam
AU - Chines, Peter S
AU - Jonsson, Anna Elisabet
AU - Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium
PY - 2014/3
Y1 - 2014/3
N2 - To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
AB - To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
KW - Alleles
KW - Asian Continental Ancestry Group
KW - Case-Control Studies
KW - Diabetes Mellitus, Type 2
KW - European Continental Ancestry Group
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Hispanic Americans
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
U2 - 10.1038/ng.2897
DO - 10.1038/ng.2897
M3 - Journal article
C2 - 24509480
VL - 46
SP - 234
EP - 244
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 3
ER -
ID: 135451038