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


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<5x10(-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.

SUBMITTER: Voight BF 

PROVIDER: S-EPMC3080658 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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

Voight Benjamin F BF   Scott Laura J LJ   Steinthorsdottir Valgerdur V   Morris Andrew P AP   Dina Christian C   Welch Ryan P RP   Zeggini Eleftheria E   Huth Cornelia C   Aulchenko Yurii S YS   Thorleifsson Gudmar G   McCulloch Laura J LJ   Ferreira Teresa T   Grallert Harald H   Amin Najaf N   Wu Guanming G   Willer Cristen J CJ   Raychaudhuri Soumya S   McCarroll Steve A SA   Langenberg Claudia C   Hofmann Oliver M OM   Dupuis Josée J   Qi Lu L   Segrè Ayellet V AV   van Hoek Mandy M   Navarro Pau P   Ardlie Kristin K   Balkau Beverley B   Benediktsson Rafn R   Bennett Amanda J AJ   Blagieva Roza R   Boerwinkle Eric E   Bonnycastle Lori L LL   Bengtsson Boström Kristina K   Bravenboer Bert B   Bumpstead Suzannah S   Burtt Noisël P NP   Charpentier Guillaume G   Chines Peter S PS   Cornelis Marilyn M   Couper David J DJ   Crawford Gabe G   Doney Alex S F AS   Elliott Katherine S KS   Elliott Amanda L AL   Erdos Michael R MR   Fox Caroline S CS   Franklin Christopher S CS   Ganser Martha M   Gieger Christian C   Grarup Niels N   Green Todd T   Griffin Simon S   Groves Christopher J CJ   Guiducci Candace C   Hadjadj Samy S   Hassanali Neelam N   Herder Christian C   Isomaa Bo B   Jackson Anne U AU   Johnson Paul R V PR   Jørgensen Torben T   Kao Wen H L WH   Klopp Norman N   Kong Augustine A   Kraft Peter P   Kuusisto Johanna J   Lauritzen Torsten T   Li Man M   Lieverse Aloysius A   Lindgren Cecilia M CM   Lyssenko Valeriya V   Marre Michel M   Meitinger Thomas T   Midthjell Kristian K   Morken Mario A MA   Narisu Narisu N   Nilsson Peter P   Owen Katharine R KR   Payne Felicity F   Perry John R B JR   Petersen Ann-Kristin AK   Platou Carl C   Proença Christine C   Prokopenko Inga I   Rathmann Wolfgang W   Rayner N William NW   Robertson Neil R NR   Rocheleau Ghislain G   Roden Michael M   Sampson Michael J MJ   Saxena Richa R   Shields Beverley M BM   Shrader Peter P   Sigurdsson Gunnar G   Sparsø Thomas T   Strassburger Klaus K   Stringham Heather M HM   Sun Qi Q   Swift Amy J AJ   Thorand Barbara B   Tichet Jean J   Tuomi Tiinamaija T   van Dam Rob M RM   van Haeften Timon W TW   van Herpt Thijs T   van Vliet-Ostaptchouk Jana V JV   Walters G Bragi GB   Weedon Michael N MN   Wijmenga Cisca C   Witteman Jacqueline J   Bergman Richard N RN   Cauchi Stephane S   Collins Francis S FS   Gloyn Anna L AL   Gyllensten Ulf U   Hansen Torben T   Hide Winston A WA   Hitman Graham A GA   Hofman Albert A   Hunter David J DJ   Hveem Kristian K   Laakso Markku M   Mohlke Karen L KL   Morris Andrew D AD   Palmer Colin N A CN   Pramstaller Peter P PP   Rudan Igor I   Sijbrands Eric E   Stein Lincoln D LD   Tuomilehto Jaakko J   Uitterlinden Andre A   Walker Mark M   Wareham Nicholas J NJ   Watanabe Richard M RM   Abecasis Gonçalo R GR   Boehm Bernhard O BO   Campbell Harry H   Daly Mark J MJ   Hattersley Andrew T AT   Hu Frank B FB   Meigs James B JB   Pankow James S JS   Pedersen Oluf O   Wichmann H-Erich HE   Barroso Inês I   Florez Jose C JC   Frayling Timothy M TM   Groop Leif L   Sladek Rob R   Thorsteinsdottir Unnur U   Wilson James F JF   Illig Thomas T   Froguel Philippe P   van Duijn Cornelia M CM   Stefansson Kari K   Altshuler David D   Boehnke Michael M   McCarthy Mark I MI  

Nature genetics 20100701 7


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<5x10(-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 l  ...[more]

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