| Literature DB >> 22325160 |
Richa Saxena1, Clara C Elbers, Yiran Guo, Inga Peter, Tom R Gaunt, Jessica L Mega, Matthew B Lanktree, Archana Tare, Berta Almoguera Castillo, Yun R Li, Toby Johnson, Marcel Bruinenberg, Diane Gilbert-Diamond, Ramakrishnan Rajagopalan, Benjamin F Voight, Ashok Balasubramanyam, John Barnard, Florianne Bauer, Jens Baumert, Tushar Bhangale, Bernhard O Böhm, Peter S Braund, Paul R Burton, Hareesh R Chandrupatla, Robert Clarke, Rhonda M Cooper-DeHoff, Errol D Crook, George Davey-Smith, Ian N Day, Anthonius de Boer, Mark C H de Groot, Fotios Drenos, Jane Ferguson, Caroline S Fox, Clement E Furlong, Quince Gibson, Christian Gieger, Lisa A Gilhuijs-Pederson, Joseph T Glessner, Anuj Goel, Yan Gong, Struan F A Grant, Diederick E Grobbee, Claire Hastie, Steve E Humphries, Cecilia E Kim, Mika Kivimaki, Marcus Kleber, Christa Meisinger, Meena Kumari, Taimour Y Langaee, Debbie A Lawlor, Mingyao Li, Maximilian T Lobmeyer, Anke-Hilse Maitland-van der Zee, Matthijs F L Meijs, Cliona M Molony, David A Morrow, Gurunathan Murugesan, Solomon K Musani, Christopher P Nelson, Stephen J Newhouse, Jeffery R O'Connell, Sandosh Padmanabhan, Jutta Palmen, Sanjey R Patel, Carl J Pepine, Mary Pettinger, Thomas S Price, Suzanne Rafelt, Jane Ranchalis, Asif Rasheed, Elisabeth Rosenthal, Ingo Ruczinski, Sonia Shah, Haiqing Shen, Günther Silbernagel, Erin N Smith, Annemieke W M Spijkerman, Alice Stanton, Michael W Steffes, Barbara Thorand, Mieke Trip, Pim van der Harst, Daphne L van der A, Erik P A van Iperen, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Bruce H R Wolffenbuttel, Taylor Young, M Hadi Zafarmand, Joseph M Zmuda, Michael Boehnke, David Altshuler, Mark McCarthy, W H Linda Kao, James S Pankow, Thomas P Cappola, Peter Sever, Neil Poulter, Mark Caulfield, Anna Dominiczak, Denis C Shields, Deepak L Bhatt, Deepak Bhatt, Li Zhang, Sean P Curtis, John Danesh, Juan P Casas, Yvonne T van der Schouw, N Charlotte Onland-Moret, Pieter A Doevendans, Gerald W Dorn, Martin Farrall, Garret A FitzGerald, Anders Hamsten, Robert Hegele, Aroon D Hingorani, Marten H Hofker, Gordon S Huggins, Thomas Illig, Gail P Jarvik, Julie A Johnson, Olaf H Klungel, William C Knowler, Wolfgang Koenig, Winfried März, James B Meigs, Olle Melander, Patricia B Munroe, Braxton D Mitchell, Susan J Bielinski, Daniel J Rader, Muredach P Reilly, Stephen S Rich, Jerome I Rotter, Danish Saleheen, Nilesh J Samani, Eric E Schadt, Alan R Shuldiner, Roy Silverstein, Kandice Kottke-Marchant, Philippa J Talmud, Hugh Watkins, Folkert W Asselbergs, Folkert Asselbergs, Paul I W de Bakker, Jeanne McCaffery, Cisca Wijmenga, Marc S Sabatine, James G Wilson, Alex Reiner, Donald W Bowden, Hakon Hakonarson, David S Siscovick, Brendan J Keating.
Abstract
To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups. Copyright ÂEntities:
Mesh：
Year: 2012 PMID： 22325160 PMCID： PMC3309185 DOI： 10.1016/j.ajhg.2011.12.022
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025