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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 C. Y. and Prokopenko, Inga, et al. (2014) In Nature Genetics 46(3). p.234-234
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... (More)
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. (Less)
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Nature Genetics
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46
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3
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234 - 234
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Nature Publishing Group
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  • wos:000332036700007
  • scopus:84895868553
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1546-1718
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10.1038/ng.2897
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English
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41a41c88-ecba-4a16-a68e-45aaef2ac8cb (old id 4363738)
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2014-04-07 09:24:37
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@article{41a41c88-ecba-4a16-a68e-45aaef2ac8cb,
  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.},
  author       = {Mahajan, Anubha and Go, Min Jin and Zhang, Weihua and Below, Jennifer E. and Gaulton, Kyle J. and Ferreira, Teresa and Horikoshi, Momoko and Johnson, Andrew D. and Ng, Maggie C. Y. and Prokopenko, Inga and Saleheen, Danish and Wang, Xu and Zeggini, Eleftheria and Abecasis, Goncalo R. and Adair, Linda S. and Almgren, Peter and Atalay, Mustafa and Aung, Tin and Baldassarre, Damiano and Balkau, Beverley and Bao, Yuqian and Barnett, Anthony H. and Barroso, Ines and Basit, Abdul and Been, Latonya F. and Beilby, John and Bell, Graeme I. and Benediktsson, Rafn and Bergman, Richard N. and Boehm, Bernhard O. and Boerwinkle, Eric and Bonnycastle, Lori L. and Burtt, Noel and Cai, Qiuyin and Campbell, Harry and Carey, Jason and Cauchi, Stephane and Caulfield, Mark and Chan, Juliana C. 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  issn         = {1546-1718},
  language     = {eng},
  number       = {3},
  pages        = {234--234},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility},
  url          = {http://dx.doi.org/10.1038/ng.2897},
  volume       = {46},
  year         = {2014},
}