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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Voight, Benjamin F.; Scott, Laura J.; Steinthorsdottir, Valgerdur; Morris, Andrew P.; Dina, Christian; Welch, Ryan P.; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S. and Thorleifsson, Gudmar, et al. (2010) In Nature Genetics 42(7). p.155-579
Abstract
By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell... (More)
By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits. (Less)
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Nature Genetics
volume
42
issue
7
pages
155 - 579
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Nature Publishing Group
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  • wos:000279242400010
  • scopus:77954143522
ISSN
1546-1718
DOI
10.1038/ng.609
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English
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yes
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e894a89f-634c-424a-9b8f-4eb5fe7a0c1e (old id 1628803)
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2010-07-21 16:53:12
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@article{e894a89f-634c-424a-9b8f-4eb5fe7a0c1e,
  abstract     = {By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P &lt; 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.},
  author       = {Voight, Benjamin F. and Scott, Laura J. and Steinthorsdottir, Valgerdur and Morris, Andrew P. and Dina, Christian and Welch, Ryan P. and Zeggini, Eleftheria and Huth, Cornelia and Aulchenko, Yurii S. and Thorleifsson, Gudmar and McCulloch, Laura J. and Ferreira, Teresa and Grallert, Harald and Amin, Najaf and Wu, Guanming and Willer, Cristen J. and Raychaudhuri, Soumya and McCarroll, Steve A. and Langenberg, Claudia and Hofmann, Oliver M. and Dupuis, Josee and Qi, Lu and Segre, Ayellet V. and van Hoek, Mandy and Navarro, Pau and Ardlie, Kristin and Balkau, Beverley and Benediktsson, Rafn and Bennett, Amanda J. and Blagieva, Roza and Boerwinkle, Eric and Bonnycastle, Lori L. and Bostrom, Kristina Bengtsson and Bravenboer, Bert and Bumpstead, Suzannah and Burtt, Noisel P. and Charpentier, Guillaume and Chines, Peter S. and Cornelis, Marilyn and Couper, David J. and Crawford, Gabe and Doney, Alex S. F. and Elliott, Katherine S. and Elliott, Amanda L. and Erdos, Michael R. and Fox, Caroline S. and Franklin, Christopher S. and Ganser, Martha and Gieger, Christian and Grarup, Niels and Green, Todd and Griffin, Simon and Groves, Christopher J. and Guiducci, Candace and Hadjadj, Samy and Hassanali, Neelam and Herder, Christian and Isomaa, Bo and Jackson, Anne U. and Johnson, Paul R. V. and Jorgensen, Torben and Kao, Wen H. L. and Klopp, Norman and Kong, Augustine and Kraft, Peter and Kuusisto, Johanna and Lauritzen, Torsten and Li, Man and Lieverse, Aloysius and Lindgren, Cecilia M. and Lyssenko, Valeriya and Marre, Michel and Meitinger, Thomas and Midthjell, Kristian and Morken, Mario A. and Narisu, Narisu and Nilsson, Peter and Owen, Katharine R. and Payne, Felicity and Perry, John R. B. and Petersen, Ann-Kristin and Platou, Carl and Proenca, Christine and Prokopenko, Inga and Rathmann, Wolfgang and Rayner, N. William and Robertson, Neil R. and Rocheleau, Ghislain and Roden, Michael and Sampson, Michael J. and Saxena, Richa and Shields, Beverley M. and Shrader, Peter and Sigurdsson, Gunnar and Sparso, Thomas and Strassburger, Klaus and Stringham, Heather M. and Sun, Qi and Swift, Amy J. and Thorand, Barbara and Tichet, Jean and Tuomi, Tiinamaija and van Dam, Rob M. and van Haeften, Timon W. and van Herpt, Thijs and van Vliet-Ostaptchouk, Jana V. and Walters, G. Bragi and Weedon, Michael N. and Wijmenga, Cisca and Witteman, Jacqueline and Bergman, Richard N. and Cauchi, Stephane and Collins, Francis S. and Gloyn, Anna L. and Gyllensten, Ulf and Hansen, Torben and Hide, Winston A. and Hitman, Graham A. and Hofman, Albert and Hunter, David J. and Hveem, Kristian and Laakso, Markku and Mohlke, Karen L. and Morris, Andrew D. and Palmer, Colin N. A. and Pramstaller, Peter P. and Rudan, Igor and Sijbrands, Eric and Stein, Lincoln D. and Tuomilehto, Jaakko and Uitterlinden, Andre and Walker, Mark and Wareham, Nicholas J. and Watanabe, Richard M. and Abecasis, Goncalo R. and Boehm, Bernhard O. and Campbell, Harry and Daly, Mark J. and Hattersley, Andrew T. and Hu, Frank B. and Meigs, James B. and Pankow, James S. and Pedersen, Oluf and Wichmann, H-Erich and Barroso, Ines and Florez, Jose C. and Frayling, Timothy M. and Groop, Leif and Sladek, Rob and Thorsteinsdottir, Unnur and Wilson, James F. and Illig, Thomas and Froguel, Philippe and van Duijn, Cornelia M. and Stefansson, Kari and Altshuler, David and Boehnke, Michael and McCarthy, Mark I.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {7},
  pages        = {155--579},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis},
  url          = {http://dx.doi.org/10.1038/ng.609},
  volume       = {42},
  year         = {2010},
}