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; Aulchenko, Yurii S.; Bf, Voight; Huth, Cornelia; McCulloch, Laura J.; Thorleifsson, Gudmar; Grallert, Harald; Amin, Najaf; Ferreira, Teresa; Wu, Guanming M.; Willer, Cristen J.; Raychaudhuri, Soumya; van Hoek, Mandy; McCarroll, Steve A.; Langenberg, Claudia; Hofmann, Oliver M.; Dupuis, Josee; Qi, Lu; Segré, Ayellet V.; Lj, Scott; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Van Hoek, M.; Benediktsson, Rafn; Bennett, Amanda J.; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori Ll; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisël P.; Bengtsson Boström, Kristina; Charpentier, Guillaume; Chines, Peter S.; Cornelis, Marilyn; Couper, David J.; Crawford, Gabe; Doney, Alex S. F.; Elliott, Katherine S.; Elliott, Amanda L.; Erdos, Michael R.; Fox, Caroline S.; Franklin, Christopher S.; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Ap, Morris; Groves, Christopher J.; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U.; Johnson, Paul R. V.; Jørgensen, Torben; Kao, Wen H. L.; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M.; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A.; Narisu, Narisu; van Dam, Rob M.; Nilsson, Peter; Rp, Welch; van Haeften, Timon W.; Owen, Katharine R.; Payne, Felicity; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V.; William Rayner, N.; Perry, John R. B.; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, Nw William; Robertson, Neil R.; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J.; Saxena, Richa; Shields, Beverley M.; Shrader, Peter; Sigurðsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M.; Sun, Qi; Swift, Amy J.; Bragi Walters, G.; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; Van Dam, R. M.; Van Haeften, T. W.; Van Herpt, T.; Van Vliet-Ostaptchouk, J.; Walters, Gb Bragi; Weedon, Michael N.; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N.; Ys, Aulchenko; Cauchi, Stéphane; Collins, Francis S.; Gloyn, Anna L.; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A.; van Duijn, Cornelia M.; Hitman, Graham A.; Hofman, Albert; Hunter, David J.; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L.; Morris, Andrew D.; Palmer, Colin N. A.; Pramstaller, Peter Pp; Jaakko, T.; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D.; Tuomilehto, Jaakko; Uitterlinden, André; Walker, Mark; Wareham, Nicholas J.; Watanabe, Richard M.; Erich Wichmann, H.; Abecasis, Gonçalo R.; Lj, McCulloch; Boehm, Bernhard O.; Campbell, Harry; Daly, Mark J.; Hattersley, Andrew T.; Hu, Frank B.; Meigs, James B.; Pankow, James S.; Pedersen, Oluf; Wichmann, He-Erich; Barroso, Inês; Florez, Jose C.; Frayling, Timothy M.; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Investigators, Magic; Wilson, James F.; Illig, Thomas; Froguel, Philippe; Van Duijn, C. M.; Stefansson, Kari; Altshuler, David; Boehnke, Michael; Consortium, Giant; McCarthy, Mark I.; Giant Consortium, Magic Investigators

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Eleftheria Zeggini
Voight et al., 2010

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@article{Voight2010,
  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;5x10(-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 Aulchenko, Yurii S. and Bf, Voight and Huth, Cornelia and McCulloch, Laura J. and Thorleifsson, Gudmar and Grallert, Harald and Amin, Najaf and Ferreira, Teresa and Wu, Guanming M. and Willer, Cristen J. and Raychaudhuri, Soumya and van Hoek, Mandy and McCarroll, Steve A. and Langenberg, Claudia and Hofmann, Oliver M. and Dupuis, Josee and Qi, Lu and Segré, Ayellet V. and Lj, Scott and Navarro, Pau and Ardlie, Kristin and Balkau, Beverley and Van Hoek, M. and Benediktsson, Rafn and Bennett, Amanda J. and Blagieva, Roza and Boerwinkle, Eric and Bonnycastle, Lori Ll and Boström, Kristina Bengtsson and Bravenboer, Bert and Bumpstead, Suzannah and Burtt, Noisël P. and Bengtsson Boström, Kristina 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 Ap, Morris 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 Jørgensen, 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 van Dam, Rob M. and Nilsson, Peter and Rp, Welch and van Haeften, Timon W. and Owen, Katharine R. and Payne, Felicity and van Herpt, Thijs and van Vliet-Ostaptchouk, Jana V. and William Rayner, N. and Perry, John R. B. and Petersen, Ann-Kristin and Platou, Carl and Proença, Christine and Prokopenko, Inga and Rathmann, Wolfgang and Rayner, Nw 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 Sigurðsson, Gunnar and Sparsø, Thomas and Strassburger, Klaus and Stringham, Heather M. and Sun, Qi and Swift, Amy J. and Bragi Walters, G. and Thorand, Barbara and Tichet, Jean and Tuomi, Tiinamaija and Van Dam, R. M. and Van Haeften, T. W. and Van Herpt, T. and Van Vliet-Ostaptchouk, J. and Walters, Gb Bragi and Weedon, Michael N. and Wijmenga, Cisca and Witteman, Jacqueline and Bergman, Richard N. and Ys, Aulchenko and Cauchi, Stéphane and Collins, Francis S. and Gloyn, Anna L. and Gyllensten, Ulf and Hansen, Torben and Hide, Winston A. and van Duijn, Cornelia M. 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 Pp and Jaakko, T. and Rudan, Igor and Sijbrands, Eric and Stein, Lincoln D. and Tuomilehto, Jaakko and Uitterlinden, André and Walker, Mark and Wareham, Nicholas J. and Watanabe, Richard M. and Erich Wichmann, H. and Abecasis, Gonçalo R. and Lj, McCulloch 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, He-Erich and Barroso, Inês and Florez, Jose C. and Frayling, Timothy M. and Groop, Leif and Sladek, Rob and Thorsteinsdottir, Unnur and Investigators, Magic and Wilson, James F. and Illig, Thomas and Froguel, Philippe and Van Duijn, C. M. and Stefansson, Kari and Altshuler, David and Boehnke, Michael and Consortium, Giant and McCarthy, Mark I. and Giant Consortium, Magic Investigators},
  doi = {10.1038/ng.609},
  month = {jun},
  title = {Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis},
  url = {http://www.nature.com/articles/ng.609.pdf},
  year = {2010}
}

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

Journal article published in 2010 by Benjamin F. Voight, Laura J. Scott, Valgerdur Steinthorsdottir, Andrew P. Morris, Christian Dina, Ryan P. Welch, Eleftheria Zeggini

, Yurii S. Aulchenko, Voight Bf, Cornelia Huth

, Laura J. McCulloch, Gudmar Thorleifsson, Harald Grallert, Najaf Amin, Teresa Ferreira and other authors. Benjamin F. Voight, Laura J. Scott, Valgerdur Steinthorsdottir, Andrew P. Morris, Christian Dina, Ryan P. Welch, Eleftheria Zeggini

, Yurii S. Aulchenko, Voight Bf, Cornelia Huth

, Laura J. McCulloch, Gudmar Thorleifsson, Harald Grallert, Najaf Amin, Teresa Ferreira, Guanming M. Wu, Cristen J. Willer, Soumya Raychaudhuri, Mandy van Hoek, Steve A. McCarroll, Claudia Langenberg, Oliver M. Hofmann, Josee Dupuis, Lu Qi, Ayellet V. Segré, Scott Lj, Pau Navarro, Kristin Ardlie, Beverley Balkau, M. Van Hoek, Rafn Benediktsson, Amanda J. Bennett, Roza Blagieva, Eric Boerwinkle, Lori Ll Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noisël P. Burtt, Kristina Bengtsson Boström, Guillaume Charpentier, Peter S. Chines, Marilyn Cornelis, David J. Couper, Gabe Crawford, Alex S. F. Doney, Katherine S. Elliott, Amanda L. Elliott, Michael R. Erdos, Caroline S. Fox, Christopher S. Franklin, Martha Ganser, Christian Gieger

, Niels Grarup

, Todd Green, Simon Griffin, Morris Ap, Christopher J. Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U. Jackson, Paul R. V. Johnson, Torben Jørgensen, Wen H. L. Kao, Norman Klopp, Augustine Kong, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M. Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A. Morken, Narisu Narisu, Rob M. van Dam, Peter Nilsson, Welch Rp, Timon W. van Haeften, Katharine R. Owen, Felicity Payne, Thijs van Herpt, Jana V. van Vliet-Ostaptchouk, N. William Rayner, John R. B. Perry, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko

, Wolfgang Rathmann, Nw William Rayner, Neil R. Robertson, Ghislain Rocheleau, Michael Roden, Michael J. Sampson, Richa Saxena, Beverley M. Shields, Peter Shrader, Gunnar Sigurðsson, Thomas Sparsø, Klaus Strassburger, Heather M. Stringham, Qi Sun, Amy J. Swift, G. Bragi Walters, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, R. M. Van Dam, T. W. Van Haeften, T. Van Herpt, J. Van Vliet-Ostaptchouk, Gb Bragi Walters, Michael N. Weedon, Cisca Wijmenga

, Jacqueline Witteman, Richard N. Bergman, Aulchenko Ys, Stéphane Cauchi, Francis S. Collins, Anna L. Gloyn, Ulf Gyllensten, Torben Hansen, Winston A. Hide

, Cornelia M. van Duijn, Graham A. Hitman, Albert Hofman, David J. Hunter, Kristian Hveem, Markku Laakso, Karen L. Mohlke, Andrew D. Morris, Colin N. A. Palmer, Peter Pp Pramstaller

, T. Jaakko, Igor Rudan, Eric Sijbrands, Lincoln D. Stein, Jaakko Tuomilehto, André Uitterlinden, Mark Walker, Nicholas J. Wareham, Richard M. Watanabe, H. Erich Wichmann, Gonçalo R. Abecasis, McCulloch Lj, Bernhard O. Boehm, Harry Campbell, Mark J. Daly, Andrew T. Hattersley, Frank B. Hu, James B. Meigs, James S. Pankow, Oluf Pedersen, He-Erich Wichmann, Inês Barroso, Jose C. Florez, Timothy M. Frayling, Leif Groop, Rob Sladek

, Unnur Thorsteinsdottir, Magic Investigators, James F. Wilson, Thomas Illig, Philippe Froguel, C. M. Van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Giant Consortium, Mark I. McCarthy, Magic Investigators Giant Consortium

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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<5x10(-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.

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

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