Title | Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Mahajan A, Go MJin, Zhang W, et al. |
Corporate Authors | DIAbetes 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 |
Journal | Nat Genet |
Volume | 46 |
Issue | 3 |
Pagination | 234-44 |
Date Published | 2014 Mar |
ISSN | 1546-1718 |
Keywords | Alleles, 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. |
DOI | 10.1038/ng.2897 |
Alternate Journal | Nat Genet |
PubMed ID | 24509480 |
PubMed Central ID | PMC3969612 |
Grant List | RG/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 |