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 CY; Prokopenko, Inga; Saleheen, Danish; Wang, Xu; Zeggini, Eleftheria; Abecasis, Goncalo R; Adair, Linda S; Almgren, Peter; Atalay, Mustafa; Aung, Tin; Baldassarre, Damiano; Balkau, Beverley

doi:https://www.dx.doi.org/10.1038/ng.2897

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Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility..pdf (647.39 KB)

Accepted version

Author(s)

Mahajan, Anubha

Go, Min Jin

Zhang, Weihua

Below, Jennifer E

Gaulton, Kyle J

more

Type

Journal Article

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.

Date Issued

2014-03-01

Date Acceptance

2014-01-17

Citation

Nature Genetics, 2014, 46 (3), pp.234-244

URI

http://hdl.handle.net/10044/1/18309

URL

https://www.nature.com/articles/ng.2897

DOI

https://www.dx.doi.org/10.1038/ng.2897

ISSN

1061-4036

Publisher

Nature Research

Start Page

234

End Page

244

Journal / Book Title

Nature Genetics

Volume

46

Issue

3

Copyright Statement

License URL

http://www.rioxx.net/licenses/all-rights-reserved

Sponsor

Medical Research Council (MRC)

National Institute for Health Research

Identifier

http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000332036700007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202

Grant Number

G0801056

G1002084

NF-SI-0611-10136

Subjects

Science & Technology

Life Sciences & Biomedicine

Genetics & Heredity

ASSOCIATION ANALYSES

GLUCOSE-HOMEOSTASIS

LOCI

VARIANTS

INDIVIDUALS

CHROMATIN

IDENTIFY

Publication Status

Published

Date Publish Online

2014-02-09