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

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

doi:10.1038/ng.609

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

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

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	Undefined/Unknown
Pages (from-to)	579-U155
Journal	Nature Genetics
Volume	42
Issue number	7
DOIs	https://doi.org/10.1038/ng.609
Publication status	Published - 2010

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Access to Document

10.1038/ng.609

http://hdl.handle.net/1765/28252

Cite this

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., ... McCarthy, MI. (2010). Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature Genetics, 42(7), 579-U155. https://doi.org/10.1038/ng.609

@article{cfd7c0d001584e3bad035664fb6340aa,

title = "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 < 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.",

author = "BF Voight and LJ Scott and V Steinthorsdottir and AP Morris and C Dina and RP Welch and E Zeggini and C Huth and YS Aulchenko and G Thorleifsson and LJ McCulloch and T Ferreira and H Grallert and Najaf Amin and GM Wu and CJ Willer and S Raychaudhuri and SA McCarroll and C Langenberg and OM Hofmann and J Dupuis and L Qi and AV Segre and {van Hoek}, Mandy and P Navarro and K Ardlie and B Balkau and R Benediktsson and AJ Bennett and R Blagieva and E Boerwinkle and LL Bonnycastle and KB Bostrom and B Bravenboer and S Bumpstead and NP Burtt and G Charpentier and PS Chines and M Cornelis and DJ Couper and G Crawford and ASF Doney and KS Elliott and AL Elliott and MR Erdos and CS Fox and CS Franklin and M Ganser and C Gieger and N Grarup and T Green and S Griffin and CJ Groves and C Guiducci and S Hadjadj and N Hassanali and Cindy Herder and B Isomaa and AU Jackson and PRV Johnson and T Jorgensen and WHL Kao and N Klopp and A Kong and P Kraft and J Kuusisto and T Lauritzen and M Li and A Lieverse and CM Lindgren and V Lyssenko and Marre, {M (Michel)} and T Meitinger and K Midthjell and MA Morken and N Narisu and P Nilsson and KR Owen and F Payne and JRB Perry and AK Petersen and C Platou and C Proenca and I Prokopenko and W Rathmann and NW Rayner and NR Robertson and G Rocheleau and M Roden and MJ Sampson and R Saxena and BM Shields and P Shrader and G Sigurdsson and T Sparso and K Strassburger and HM Stringham and Q Sun and AJ Swift and B Thorand and J Tichet and T Tuomi and {van Dam}, RM and {van Haeften}, TW and {van Herpt}, T and {van Vliet-Ostaptchouk}, JV and GB Walters and MN Weedon and C Wijmenga and JCM Witteman and RN Bergman and S Cauchi and FS Collins and AL Gloyn and U Gyllensten and T Hansen and WA Hide and GA Hitman and Bert Hofman and DJ Hunter and K Hveem and M Laakso and KL Mohlke and AD Morris and CNA Palmer and PP Pramstaller and I Rudan and E.J.G. Sijbrands and LD Stein and T Jaakko and Andr{\'e} Uitterlinden and M Walker and NJ Wareham and RM Watanabe and GR Abecasis and BO Boehm and H Campbell and MJ Daly and AT Hattersley and FB Hu and JB Meigs and JS Pankow and O Pedersen and HE Wichmann and I Barroso and JC Florez and TM Frayling and L Groop and R Sladek and U Thorsteinsdottir and JF Wilson and T Illig and P Froguel and Cornelia Duijn and K Stefansson and D Altshuler and M Boehnke and MI McCarthy",

year = "2010",

doi = "10.1038/ng.609",

language = "Undefined/Unknown",

volume = "42",

pages = "579--U155",

journal = "Nature Genetics",

issn = "1061-4036",

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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, JCM, Bergman, RN, Cauchi, S, Collins, FS, Gloyn, AL, Gyllensten, U, Hansen, T, Hide, WA, Hitman, GA, Hofman, B, Hunter, DJ, Hveem, K, Laakso, M, Mohlke, KL, Morris, AD, Palmer, CNA, Pramstaller, PP, Rudan, I, Sijbrands, EJG, 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, Duijn, C, Stefansson, K, Altshuler, D, Boehnke, M & McCarthy, MI 2010, 'Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis', Nature Genetics, vol. 42, no. 7, pp. 579-U155. https://doi.org/10.1038/ng.609

TY - JOUR

T1 - Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

AU - Voight, BF

AU - Scott, LJ

AU - Steinthorsdottir, V

AU - Morris, AP

AU - Dina, C

AU - Welch, RP

AU - Zeggini, E

AU - Huth, C

AU - Aulchenko, YS

AU - Thorleifsson, G

AU - McCulloch, LJ

AU - Ferreira, T

AU - Grallert, H

AU - Amin, Najaf

AU - Wu, GM

AU - Willer, CJ

AU - Raychaudhuri, S

AU - McCarroll, SA

AU - Langenberg, C

AU - Hofmann, OM

AU - Dupuis, J

AU - Qi, L

AU - Segre, AV

AU - van Hoek, Mandy

AU - Navarro, P

AU - Ardlie, K

AU - Balkau, B

AU - Benediktsson, R

AU - Bennett, AJ

AU - Blagieva, R

AU - Boerwinkle, E

AU - Bonnycastle, LL

AU - Bostrom, KB

AU - Bravenboer, B

AU - Bumpstead, S

AU - Burtt, NP

AU - Charpentier, G

AU - Chines, PS

AU - Cornelis, M

AU - Couper, DJ

AU - Crawford, G

AU - Doney, ASF

AU - Elliott, KS

AU - Elliott, AL

AU - Erdos, MR

AU - Fox, CS

AU - Franklin, CS

AU - Ganser, M

AU - Gieger, C

AU - Grarup, N

AU - Green, T

AU - Griffin, S

AU - Groves, CJ

AU - Guiducci, C

AU - Hadjadj, S

AU - Hassanali, N

AU - Herder, Cindy

AU - Isomaa, B

AU - Jackson, AU

AU - Johnson, PRV

AU - Jorgensen, T

AU - Kao, WHL

AU - Klopp, N

AU - Kong, A

AU - Kraft, P

AU - Kuusisto, J

AU - Lauritzen, T

AU - Li, M

AU - Lieverse, A

AU - Lindgren, CM

AU - Lyssenko, V

AU - Marre, M (Michel)

AU - Meitinger, T

AU - Midthjell, K

AU - Morken, MA

AU - Narisu, N

AU - Nilsson, P

AU - Owen, KR

AU - Payne, F

AU - Perry, JRB

AU - Petersen, AK

AU - Platou, C

AU - Proenca, C

AU - Prokopenko, I

AU - Rathmann, W

AU - Rayner, NW

AU - Robertson, NR

AU - Rocheleau, G

AU - Roden, M

AU - Sampson, MJ

AU - Saxena, R

AU - Shields, BM

AU - Shrader, P

AU - Sigurdsson, G

AU - Sparso, T

AU - Strassburger, K

AU - Stringham, HM

AU - Sun, Q

AU - Swift, AJ

AU - Thorand, B

AU - Tichet, J

AU - Tuomi, T

AU - van Dam, RM

AU - van Haeften, TW

AU - van Herpt, T

AU - van Vliet-Ostaptchouk, JV

AU - Walters, GB

AU - Weedon, MN

AU - Wijmenga, C

AU - Witteman, JCM

AU - Bergman, RN

AU - Cauchi, S

AU - Collins, FS

AU - Gloyn, AL

AU - Gyllensten, U

AU - Hansen, T

AU - Hide, WA

AU - Hitman, GA

AU - Hofman, Bert

AU - Hunter, DJ

AU - Hveem, K

AU - Laakso, M

AU - Mohlke, KL

AU - Morris, AD

AU - Palmer, CNA

AU - Pramstaller, PP

AU - Rudan, I

AU - Sijbrands, E.J.G.

AU - Stein, LD

AU - Jaakko, T

AU - Uitterlinden, André

AU - Walker, M

AU - Wareham, NJ

AU - Watanabe, RM

AU - Abecasis, GR

AU - Boehm, BO

AU - Campbell, H

AU - Daly, MJ

AU - Hattersley, AT

AU - Hu, FB

AU - Meigs, JB

AU - Pankow, JS

AU - Pedersen, O

AU - Wichmann, HE

AU - Barroso, I

AU - Florez, JC

AU - Frayling, TM

AU - Groop, L

AU - Sladek, R

AU - Thorsteinsdottir, U

AU - Wilson, JF

AU - Illig, T

AU - Froguel, P

AU - Duijn, Cornelia

AU - Stefansson, K

AU - Altshuler, D

AU - Boehnke, M

AU - McCarthy, MI

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1038/ng.609

DO - 10.1038/ng.609

M3 - Article

C2 - 20581827

SN - 1061-4036

VL - 42

SP - 579-U155

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -