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

Lookup NU author(s): Professor Mark Walker

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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 < 5 x 10(-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.


Publication metadata

Author(s): Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu GM, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, Segre AV, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Bostrom KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney ASF, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PRV, Jorgensen T, Kao WHL, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JRB, Petersen AK, Platou C, Proenca C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparso T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet-Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CNA, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Jaakko T, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Altshuler D, Boehnke M, McCarthy MI, MAGIC Investigators, GIANT Consortium

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2010

Volume: 42

Issue: 7

Pages: 579-589

Print publication date: 27/06/2010

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.609

DOI: 10.1038/ng.609


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Funding

Funder referenceFunder name
064890Wellcome Trust
072960Wellcome Trust
077016Wellcome Trust
079557Wellcome Trust
083270Wellcome Trust
088885Wellcome Trust
090532Wellcome Trust
075491Wellcome Trust
076113Wellcome Trust
081682Wellcome Trust
086596Wellcome Trust
1K08AR055688NIAMS NIH HHS
1K99HL094535-01A1NHLBI NIH HHS
DHCS/07/07/008Department of Health
DK069922NIDDK NIH HHS
DK072193NIDDK NIH HHS
DK58845NIDDK NIH HHS
CZB/4/710Chief Scientist Office
DK062370NIDDK NIH HHS
DK073490NIDDK NIH HHS
DK078616NIDDK NIH HHS
G0700222(81696)Medical Research Council
HHSN268200625226CPHS HHS
G0600331Medical Research Council
G0601261Medical Research Council
G0700222Medical Research Council
G0701863Medical Research Council
K08 AR055688-03NIAMS NIH HHS
K24-DK080140NIDDK NIH HHS
MC_U106179474Medical Research Council
K08 AR055688NIAMS NIH HHS
K23 DK065978NIDDK NIH HHS
K23-DK65978NIDDK NIH HHS
K24 DK080140NIDDK NIH HHS
K99 HL094535NHLBI NIH HHS
N01HC25195NHLBI NIH HHS
N01-HC-25195NHLBI NIH HHS
N01HC55015NHLBI NIH HHS
N01-HC-55015NHLBI NIH HHS
N01HC55016NHLBI NIH HHS
N01-HC-55016NHLBI NIH HHS
N01HC55018NHLBI NIH HHS
N01-HC-55018NHLBI NIH HHS
N01HC55020NHLBI NIH HHS
N01-HC-55020NHLBI NIH HHS
N01HC55022NHLBI NIH HHS
N01-HC-55022NHLBI NIH HHS
MC_U106179471Medical Research Council
MC_U127592696Medical Research Council
N01HC55019NHLBI NIH HHS
N01-HC-55019NHLBI NIH HHS
N01HC55021NHLBI NIH HHS
N01-HC-55021NHLBI NIH HHS
R01 DK058845NIDDK NIH HHS
R01 DK073490NIDDK NIH HHS
N02-HL-6-4278NHLBI NIH HHS
R01 HL086694NHLBI NIH HHS
R01 HL087641NHLBI NIH HHS
R01HL086694NHLBI NIH HHS
R01HL087641NHLBI NIH HHS
R56 DK062370NIDDK NIH HHS
R01 DK029867NIDDK NIH HHS
R01 DK062370NIDDK NIH HHS
R01 DK069922NIDDK NIH HHS
R01 DK072193NIDDK NIH HHS
R01 DK078616NIDDK NIH HHS
U01 HG004402NHGRI NIH HHS
R01 HL059367NHLBI NIH HHS
U01HG004399NHGRI NIH HHS
UL1RR025005NCRR NIH HHS
R01HL59367NHLBI NIH HHS
U01 DK062370NIDDK NIH HHS
U01 DK078616NIDDK NIH HHS
U01 HG004171NHGRI NIH HHS
U01 HG004399NHGRI NIH HHS
U01HG004171NHGRI NIH HHS
U01HG004402NHGRI NIH HHS
U54 DA021519NIDA NIH HHS
UL1 RR025005NCRR NIH HHS
Z01 HG000024NHGRI NIH HHS

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