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

Article


Diagram, Consortium, AGEN-T2D, Consortium, SAT2D, Consortium, MAT2D, Consortium, T2D-GENES, Consortium and Pinidiyapathirage, Janani M.. 2014. "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility." Nature Genetics. 46 (3), pp. 234-244. https://doi.org/10.1038/ng.2897
Article Title

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

ERA Journal ID16629
Article CategoryArticle
AuthorsDiagram, Consortium (Author), AGEN-T2D, Consortium (Author), SAT2D, Consortium (Author), MAT2D, Consortium (Author), T2D-GENES, Consortium (Author) and Pinidiyapathirage, Janani M. (Author)
Journal TitleNature Genetics
Journal Citation46 (3), pp. 234-244
Number of Pages10
Year2014
Place of PublicationUnited States
ISSN1061-4036
1546-1718
Digital Object Identifier (DOI)https://doi.org/10.1038/ng.2897
Web Address (URL)https://www.nature.com/articles/ng.2897
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 significant excess in 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 novel T2D susceptibility loci. Furthermore, we observed considerable improvements in 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 characterisation 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.

KeywordsType 2 diabetes, Genome-wide,high density lipoprotein cholesterol; triacylglycerol
Contains Sensitive ContentDoes not contain sensitive content
ANZSRC Field of Research 2020310505. Gene expression (incl. microarray and other genome-wide approaches)
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Byline AffiliationsMultiple International Universities
Asian Genetic Epidemiology Network, China
SAT2D Consortium
IMSS General Regional Hospital 1, Mexico
T2D Genes Consortium, United States
University of Kelaniya, Sri Lanka
Institution of OriginUniversity of Southern Queensland
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