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

Journal article

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.

Authors: Mahajan, A; Go, M; Zhang, W; Below, J; Gaulton, K

• Publication status: Published
• Journal: Nature genetics
• Volume: 46
• Issue: 3
• Pages: 234-244
• Publication date: 2014-03-01
• DOI: 10.1038/ng.2897
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Hispanic Americans; Humans; European Continental Ancestry Group; Genetic Predisposition to Disease; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; Risk Factors; South Asian Type 2 Diabetes (SAT2D) Consortium; Case-Control Studies; Genome-Wide Association Study; Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium; Polymorphism, Single Nucleotide; Alleles; Asian Continental Ancestry Group; Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium; Mexican American Type 2 Diabetes (MAT2D) Consortium; Diabetes Mellitus, Type 2