Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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Saxena, R; Elbers, CC; Guo, Y; Peter, I; Gaunt, TR; Mega, JL; Lanktree, MB; Tare, A; Castillo, BA; Li, YR; Johnson, T; Bruinenberg, M; Gilbert-Diamond, D; Rajagopalan, R; Voight, BF; Balasubramanyam, A; Barnard, J; Bauer, F; Baumert, J; Bhangale, T; Böhm, BO; Braund, PS; Burton, PR; Chandrupatla, HR; Clarke, R; Cooper-DeHoff, RM; Crook, ED; Davey-Smith, G; Day, IN; de Boer, A; de Groot, MC; Drenos, F; Ferguson, J; Fox, CS; Furlong, CE; Gibson, Q; Gieger, C; Gilhuijs-Pederson, LA; Glessner, JT; Goel, A; Gong, Y; Grant, SF; Grobbee, DE; Hastie, C; Humphries, SE; Kim, CE; Kivimaki, M; Kleber, M; Meisinger, C; Kumari, M; Langaee, TY; Lawlor, DA; Li, M; Lobmeyer, MT; Maitland-van der Zee, AH; Meijs, MF; Molony, CM; Morrow, DA; Murugesan, G; Musani, SK; Nelson, CP; Newhouse, SJ; O'Connell, JR; Padmanabhan, S; Palmen, J; Patel, SR; Pepine, CJ; Pettinger, M; Price, TS; Rafelt, S; Ranchalis, J; Rasheed, A; Rosenthal, E; Ruczinski, I; Shah, S; Shen, H; Silbernagel, G; Smith, EN; Spijkerman, AW; Stanton, A; Steffes, MW; Thorand, B; Trip, M; van der Harst, P; van der A, DL; van Iperen, EP; van Setten, J; van Vliet-Ostaptchouk, JV; Verweij, N; Wolffenbuttel, BH; Young, T; Zafarmand, MH; Zmuda, JM; Look AHEAD Research Group; DIAGRAM consortium; Boehnke, M; Altshuler, D; McCarthy, M; Kao, WH; Pankow, JS; Cappola, TP; Sever, P; Poulter, N; Caulfield, M; Dominiczak, A; Shields, DC; Bhatt, DL; Bhatt, D; Zhang, L; Curtis, SP; Danesh, J; Casas, JP; van der Schouw, YT; Onland-Moret, NC; Doevendans, PA; Dorn, GW; Farrall, M; FitzGerald, GA; Hamsten, A; Hegele, R; Hingorani, AD; Hofker, MH; Huggins, GS; Illig, T; Jarvik, GP; Johnson, JA; Klungel, OH; Knowler, WC; Koenig, W; März, W; Meigs, JB; Melander, O; Munroe, PB; Mitchell, BD; Bielinski, SJ; Rader, DJ; Reilly, MP; Rich, SS; Rotter, JI; Saleheen, D; Samani, NJ; Schadt, EE; Shuldiner, AR; Silverstein, R; Kottke-Marchant, K; Talmud, PJ; Watkins, H; Asselbergs, FW; Asselbergs, F; de Bakker, PI; McCaffery, J; Wijmenga, C; Sabatine, MS; Wilson, JG; Reiner, A; Bowden, DW; Hakonarson, H; Siscovick, DS; Keating, BJ.
Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.
Am J Hum Genet. 2012; 90(3):410-425
Doi: 10.1016/j.ajhg.2011.12.022
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- Co-Autor*innen der Med Uni Graz
- März Winfried
- Silbernagel Günther
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- 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 © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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- Adolescent -
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- Diabetes Mellitus, Type 2 - ethnology Diabetes Mellitus, Type 2 - genetics
- Ethnic Groups -
- Female -
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- Genetic Loci -
- Genetic Predisposition to Disease -
- Genome-Wide Association Study - methods
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