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Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

TitleGenome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
Publication TypeJournal Article
Year of Publication2014
AuthorsMahajan A, Go MJin, Zhang W, et al.
Corporate AuthorsDIAbetes Genetics Replication and Meta-analysis(DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes(AGEN-T2D) Consortium, South Asian Type 2 Diabetes(SAT2D) Consortium, Mexican American Type 2 Diabetes(MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples(T2D-GENES) Consortium
JournalNat Genet
Volume46
Issue3
Pagination234-44
Date Published2014 Mar
ISSN1546-1718
KeywordsAlleles, Asian Continental Ancestry Group, Case-Control Studies, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic Americans, Humans, Polymorphism, Single Nucleotide, Risk Factors
Abstract

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.

DOI10.1038/ng.2897
Alternate JournalNat Genet
PubMed ID24509480
PubMed Central IDPMC3969612
Grant ListRG/08/008/25291 / BHF_ / British Heart Foundation / United Kingdom
MC_UP_A100_1003 / MRC_ / Medical Research Council / United Kingdom
UL1 TR001079 / TR / NCATS NIH HHS / United States
R01 HG000376 / HG / NHGRI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom
K24 DK080140 / DK / NIDDK NIH HHS / United States
DK062370 / DK / NIDDK NIH HHS / United States
MR/K006584/1 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/5 / MRC_ / Medical Research Council / United Kingdom
WT085475 / WT_ / Wellcome Trust / United Kingdom
R01 DK093757 / DK / NIDDK NIH HHS / United States
U01 DK085501 / DK / NIDDK NIH HHS / United States
R01 DK078616 / DK / NIDDK NIH HHS / United States
WT081682 / WT_ / Wellcome Trust / United Kingdom
CZB/4/710 / CSO_ / Chief Scientist Office / United Kingdom
G9521010 / MRC_ / Medical Research Council / United Kingdom
098017 / WT_ / Wellcome Trust / United Kingdom
G0801056 / MRC_ / Medical Research Council / United Kingdom
095552 / WT_ / Wellcome Trust / United Kingdom
U01 DK085545 / DK / NIDDK NIH HHS / United States
DK073541 / DK / NIDDK NIH HHS / United States
RG/08/014/24067 / BHF_ / British Heart Foundation / United Kingdom
R01 DK072193 / DK / NIDDK NIH HHS / United States
/ CAPMC / CIHR / Canada
MR/L003120/1 / MRC_ / Medical Research Council / United Kingdom
R56 HG000376 / HG / NHGRI NIH HHS / United States
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
R01 DK062370 / DK / NIDDK NIH HHS / United States
MC_U106179471 / MRC_ / Medical Research Council / United Kingdom
R01 DK073541 / DK / NIDDK NIH HHS / United States
G1002084 / MRC_ / Medical Research Council / United Kingdom
MC_PC_U127592696 / MRC_ / Medical Research Council / United Kingdom
090532 / WT_ / Wellcome Trust / United Kingdom
U01 DK085584 / DK / NIDDK NIH HHS / United States
DK085584 / DK / NIDDK NIH HHS / United States
DK085545 / DK / NIDDK NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
DK085501 / DK / NIDDK NIH HHS / United States
WT090367 / WT_ / Wellcome Trust / United Kingdom
098381 / WT_ / Wellcome Trust / United Kingdom
R24 HD050924 / HD / NICHD NIH HHS / United States
G0601261 / MRC_ / Medical Research Council / United Kingdom
HG000376 / HG / NHGRI NIH HHS / United States