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| Content Provider | PubMed Central |
|---|---|
| Author | Saxena, Richa Elbers, Clara C. Guo, Yiran Peter, Inga Gaunt, Tom R. Mega, Jessica L. Lanktree, Matthew B. Tare, Archana Castillo, Berta Almoguera Li, Yun R. Johnson, Toby Bruinenberg, Marcel Diane, Gilbert-diamond Rajagopalan, Ramakrishnan Voight, Benjamin F. Balasubramanyam, Ashok Barnard, John Bauer, Florianne Baumert, Jens Tushar, Bhangale Böhm, Bernhard O. Braund, Peter S. Burton, Paul R. Chandrupatla, Hareesh R. Clarke, Robert Cooper-dehoff, Rhonda M. Crook, Errol D. George, Davey-smith Day, Ian N. Boer, Anthonius De Groot, Mark C. H. De Drenos, Fotios Ferguson, Jane Fox, Caroline S. Furlong, Clement E. Gibson, Quince Gieger, Christian Gilhuijs-pederson, Lisa A. Glessner, Joseph T. Goel, Anuj Gong, Yan Grant, Struan F. A. Grobbee, Diederick E. Hastie, Claire Humphries, Steve E. Kim, Cecilia E. Kivimaki, Mika Kleber, Marcus Meisinger, Christa Kumari, Meena Langaee, Taimour Y. Lawlor, Debbie A. Li, Mingyao Lobmeyer, Maximilian T. Zee, Anke-hilse Maitland-van Der Meijs, Matthijs F. L. Molony, Cliona M. Morrow, David A. Murugesan, Gurunathan Musani, Solomon K. Nelson, Christopher P. Newhouse, Stephen J. O'connell, Jeffery R. Padmanabhan, Sandosh Palmen, Jutta Patel, Sanjey R. Pepine, Carl J. Pettinger, Mary Price, Thomas S. Suzanne, Rafelt Jane, Ranchalis Rasheed, Asif Rosenthal, Elisabeth Ingo, Ruczinski Shah, Sonia Shen, Haiqing Silbernagel, Günther Smith, Erin N. Spijkerman, Annemieke W. M. Stanton, Alice Steffes, Michael W. Barbara, Thorand Trip, Mieke Harst, Pim Van Der Van, Der A. Daphne L. Van, Iperen Erik P. A. Setten, Jessica Van Van, Vliet-ostaptchouk Jana V. Verweij, Niek Wolffenbuttel, Bruce H. R. Young, Taylor Hadi, Zafarmand M. Zmuda, Joseph M. Boehnke, Michael Altshuler, David Mccarthy, Mark Kao, W. H. Linda Pankow, James S. Cappola, Thomas P. Sever, Peter Poulter, Neil Caulfield, Mark Dominiczak, Anna Shields, Denis C. Bhatt, Deepak L. Zhang, Li Curtis, Sean P. Danesh, John Casas, Juan P. Schouw, Yvonne T. Van Der Charlotte, Onland-moret N. Doevendans, Pieter A. Dorn, Gerald W. Farrall, Martin Fitzgerald, Garret A. Anders, Hamsten Robert, Hegele Hingorani, Aroon D. Hofker, Marten H. Huggins, Gordon S. Illig, Thomas Jarvik, Gail P. Johnson, Julie A. Klungel, Olaf H. Knowler, William C. Koenig, Wolfgang März, Winfried Meigs, James B. Melander, Olle Munroe, Patricia B. Mitchell, Braxton D. Bielinski, Susan J. Rader, Daniel J. Reilly, Muredach P. Rich, Stephen S. Rotter, Jerome I. Danish, Saleheen Samani, Nilesh J. Schadt, Eric E. Shuldiner, Alan R. Silverstein, Roy Kottke-marchant, Kandice Talmud, Philippa J. Watkins, Hugh Asselbergs, Folkert W. Bakker, Paul I. W. De Mccaffery, Jeanne Wijmenga, Cisca Sabatine, Marc S. Wilson, James G. Reiner, Alex Bowden, Donald W. Hakonarson, Hakon Siscovick, David S. Keating, Brendan J. |
| Copyright Year | 2012 |
| 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. |
| Related Links | http://dx.doi.org/10.1016/j.ajhg.2011.12.022 |
| Ending Page | 425 |
| Page Count | 16 |
| Starting Page | 410 |
| File Format | |
| ISSN | 00029297 |
| e-ISSN | 15376605 |
| Journal | American Journal of Human Genetics |
| Issue Number | 3 |
| Volume Number | 90 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-03-01 |
| Access Restriction | Open |
| Rights Holder | Elsevier |
| Subject Keyword | Genetics(clinical) Genetics Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
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