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Am J Hum Genet DOI:10.1016/j.ajhg.2011.12.022

Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

Publication TypeJournal Article
Year of Publication2012
AuthorsSaxena, R, Elbers, CC, Guo, Y, Peter, I, Gaunt, TR, Mega, JL, Lanktree, MB, Tare, A, Castillo, BAlmoguera, 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, MCH, Drenos, F, Ferguson, J, Fox, CS, Furlong, CE, Gibson, Q, Gieger, C, Gilhuijs-Pederson, LA, Glessner, JT, Goel, A, Gong, Y, Grant, SFA, Grobbee, DE, Hastie, C, Humphries, SE, Kim, CE, Kivimaki, M, Kleber, M, Meisinger, C, Kumari, M, Langaee, TY, Lawlor, DA, Li, M, Lobmeyer, MT, van der Zee, A-HMaitland-, Meijs, MFL, 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, AWM, Stanton, A, Steffes, MW, Thorand, B, Trip, M, van der Harst, P, van der A, DL, van Iperen, EPA, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N, Wolffenbuttel, BHR, Young, T, M Zafarmand, H, Zmuda, JM, Boehnke, M, Altshuler, D, McCarthy, M, Kao, WHLinda, 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, N Onland-Moret, C, 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, PIW, McCaffery, J, Wijmenga, C, Sabatine, MS, Wilson, JG, Reiner, A, Bowden, DW, Hakonarson, H, Siscovick, DS, Keating, BJ
Corporate AuthorsLook AHEAD Research Group, DIAGRAM consortium
JournalAm J Hum Genet
Volume90
Issue3
Pages410-25
Date Published2012 Mar 09
ISSN1537-6605
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Diabetes Mellitus, Type 2, Ethnic Groups, Female, Follow-Up Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Young Adult
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

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0002-9297(12)00031-6
DOI10.1016/j.ajhg.2011.12.022
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22325160?dopt=Abstract

Alternate JournalAm. J. Hum. Genet.
PubMed ID22325160
PubMed Central IDPMC3309185
Grant ListG9521010 / / Medical Research Council / United Kingdom
PG/09/022/26739 / / British Heart Foundation / United Kingdom
RG/08/008/25291 / / British Heart Foundation / United Kingdom
G0600705 / / Medical Research Council / United Kingdom
G19/35 / / Medical Research Council / United Kingdom
G0100222 / / Medical Research Council / United Kingdom
U01 GM074492 / GM / NIGMS NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
G8802774 / / Medical Research Council / United Kingdom
G0902037 / / Medical Research Council / United Kingdom
UL1 TR000124 / TR / NCATS NIH HHS / United States
MC_U137686857 / / Medical Research Council / United Kingdom
R01 HL074730 / HL / NHLBI NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
N01HC65226 / HL / NHLBI NIH HHS / United States
R01 HL088577 / HL / NHLBI NIH HHS / United States
R21 DK089378 / DK / NIDDK NIH HHS / United States
RG/08/014/24067 / / British Heart Foundation / United Kingdom
P30 DK017047 / DK / NIDDK NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States
RG/07/008/23674 / / British Heart Foundation / United Kingdom
RG/10/12/28456 / / British Heart Foundation / United Kingdom