New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

J Dupuis; C Langenberg; I Prokopenko; R Saxena; N Soranzo; AU Jackson; E Wheeler; NL Glazer; N Bouatia-Naji; AL Gloyn; CM Lindgren; R Magi; AP Morris; J Randall; T Johnson; P Elliott; D Rybin; G Thorleifsson; V Steinthorsdottir; Peter Henneman; H Grallert; Abbas Dehghan; JJ (Jouke Jan) Hottenga; CS Franklin; P Navarro; K Song; A Goel; JRB Perry; JM Egan; T Lajunen; N Grarup; T Sparso; A Doney; BF Voight; HM Stringham; M Li; S Kanoni; P Shrader; C Cavalcanti-Proenca; M Kumari; L Qi; NJ Timpson; C Gieger; C Zabena; G Rocheleau; E Ingelsson; P An; J O'Connell; J Luan; A Elliott; SA McCarroll; F Payne; RM Roccasecca; F Pattou; P Sethupathy; K Ardlie; Y (Yavuz) Ariyurek; B Balkau; P Barter; JP Beilby; Y Ben-Shlomo; R Benediktsson; AJ Bennett; S Bergmann; M Bochud; E Boerwinkle; A Bonnefond; LL Bonnycastle; K Borch-Johnsen; Y Bottcher; E Brunner; SJ Bumpstead; G Charpentier; YDI Chen; P Chines; R Clarke; LJM Coin; MN Cooper; M Cornelis; G Crawford; L Crisponi; INM Day; EJC de Geus; J Delplanque; C Dina; MR Erdos; AC Fedson; A Fischer-Rosinsky; NG Forouhi; CS Fox; R Frants; MG Franzosi; P Galan; MO Goodarzi; J Graessler; CJ Groves; S Grundy; R Gwilliam; U Gyllensten; S Hadjadj; G Hallmans; N Hammond; XJ Han; AL Hartikainen; N Hassanali; C Hayward; SC Heath; S Hercberg; Cindy Herder; AA Hicks; DR Hillman; AD Hingorani; Bert Hofman; J Hui; J Hung; B Isomaa; PRV Johnson; T Jorgensen; A Jula; M Kaakinen; J Kaprio; YA Kesaniemi; M Kivimaki; B Knight; S Koskinen; P Kovacs; KO Kyvik; GM Lathrop; DA Lawlor; O Le Bacquer; C Lecoeur; Yunlei Li; V Lyssenko; R Mahley; M Mangino; AK Manning; MT Martinez-Larrad; JB McAteer; LJ McCulloch; R McPherson; C Meisinger; D Melzer; D Meyre; BD Mitchell; MA Morken; S Mukherjee; S Naitza; N Narisu; MJ Neville; Ben Oostra; M Orru; R Pakyz; CNA Palmer; G Paolisso; C Pattaro; D Pearson; JF Peden; NL Pedersen; M Perola; AFH Pfeiffer; I Pichler; O Polasek; D Posthuma; SC Potter; A Pouta; MA Province; BM Psaty; W Rathmann; NW Rayner; K Rice; S Ripatti; Fernando Rivadeneira; M Roden; O Rolandsson; A Sandbaek; M Sandhu; S Sanna; AA Sayer; P Scheet; LJ Scott; U Seedorf; SJ Sharp; B Shields; G Sigurosson; E.J.G. Sijbrands; A Silveira; L Simpson; A Singleton; NL Smith; U Sovio; A Swift; H Syddall; AC Syvanen; T Tanaka; B Thorand; J Tichet; A Tonjes; T Tuomi; André Uitterlinden; KW van Dijk; Mandy van Hoek; D Varma; S Visvikis-Siest; V Vitart; N Vogelzangs; G Waeber; PJ Wagner; A Walley; GB Walters; KL Ward; H Watkins; MN Weedon; SH Wild; G Willemsen; JCM Witteman; JWG Yarnell; E Zeggini; D Zelenika; B Zethelius; GJ Zhai; JH Zhao; M.C. Zillikens; IB Borecki; RJF Loos; P Meneton; PKE Magnusson; DM Nathan; GH Williams; AT Hattersley; K Silander; V Salomaa; GD Smith; SR Bornstein; P Schwarz; J Spranger; F Karpe; AR Shuldiner; C Cooper; GV Dedoussis; M Serrano-Rios; AD Morris; L Lind; LJ Palmer; FB Hu; PW Franks; S Ebrahim; M Marmot; WHL Kao; JS Pankow; MJ Sampson; J Kuusisto; M Laakso; O Pedersen; PP Pramstaller; HE Wichmann; T Illig; I Rudan; AF Wright; M Stumvoll; H Campbell; JF Wilson; RN Bergman; TA Buchanan; FS Collins; KL Mohlke; J Tuomilehto; TT Valle; D Altshuler; JI Rotter; DS Siscovick; BWJH Penninx; DI Boomsma; P Deloukas; TD Spector; TM Frayling; L Ferrucci; A Kong; U Thorsteinsdottir; K Stefansson; Cornelia Duijn; YS Aulchenko; A Cao; A Scuteri; D Schlessinger; M Uda; A Ruokonen; MR Jarvelin; DM Waterworth; P Vollenweider; L Peltonen; V Mooser; GR Abecasis; NJ Wareham; R Sladek; P Froguel; RM Watanabe; JB Meigs; L Groop; M Boehnke; MI McCarthy; JC Florez; I Barroso; T Hansen

doi:10.1038/ng.520

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

J Dupuis, C Langenberg, I Prokopenko, R Saxena, N Soranzo, AU Jackson, E Wheeler, NL Glazer, N Bouatia-Naji, AL Gloyn, CM Lindgren, R Magi, AP Morris, J Randall, T Johnson, P Elliott, D Rybin, G Thorleifsson, V Steinthorsdottir, Peter HennemanH Grallert, Abbas Dehghan, JJ (Jouke Jan) Hottenga, CS Franklin, P Navarro, K Song, A Goel, JRB Perry, JM Egan, T Lajunen, N Grarup, T Sparso, A Doney, BF Voight, HM Stringham, M Li, S Kanoni, P Shrader, C Cavalcanti-Proenca, M Kumari, L Qi, NJ Timpson, C Gieger, C Zabena, G Rocheleau, E Ingelsson, P An, J O'Connell, J Luan, A Elliott, SA McCarroll, F Payne, RM Roccasecca, F Pattou, P Sethupathy, K Ardlie, Y (Yavuz) Ariyurek, B Balkau, P Barter, JP Beilby, Y Ben-Shlomo, R Benediktsson, AJ Bennett, S Bergmann, M Bochud, E Boerwinkle, A Bonnefond, LL Bonnycastle, K Borch-Johnsen, Y Bottcher, E Brunner, SJ Bumpstead, G Charpentier, YDI Chen, P Chines, R Clarke, LJM Coin, MN Cooper, M Cornelis, G Crawford, L Crisponi, INM Day, EJC de Geus, J Delplanque, C Dina, MR Erdos, AC Fedson, A Fischer-Rosinsky, NG Forouhi, CS Fox, R Frants, MG Franzosi, P Galan, MO Goodarzi, J Graessler, CJ Groves, S Grundy, R Gwilliam, U Gyllensten, S Hadjadj, G Hallmans, N Hammond, XJ Han, AL Hartikainen, N Hassanali, C Hayward, SC Heath, S Hercberg, Cindy Herder, AA Hicks, DR Hillman, AD Hingorani, Bert Hofman, J Hui, J Hung, B Isomaa, PRV Johnson, T Jorgensen, A Jula, M Kaakinen, J Kaprio, YA Kesaniemi, M Kivimaki, B Knight, S Koskinen, P Kovacs, KO Kyvik, GM Lathrop, DA Lawlor, O Le Bacquer, C Lecoeur, Yunlei Li, V Lyssenko, R Mahley, M Mangino, AK Manning, MT Martinez-Larrad, JB McAteer, LJ McCulloch, R McPherson, C Meisinger, D Melzer, D Meyre, BD Mitchell, MA Morken, S Mukherjee, S Naitza, N Narisu, MJ Neville, Ben Oostra, M Orru, R Pakyz, CNA Palmer, G Paolisso, C Pattaro, D Pearson, JF Peden, NL Pedersen, M Perola, AFH Pfeiffer, I Pichler, O Polasek, D Posthuma, SC Potter, A Pouta, MA Province, BM Psaty, W Rathmann, NW Rayner, K Rice, S Ripatti, Fernando Rivadeneira, M Roden, O Rolandsson, A Sandbaek, M Sandhu, S Sanna, AA Sayer, P Scheet, LJ Scott, U Seedorf, SJ Sharp, B Shields, G Sigurosson, E.J.G. Sijbrands, A Silveira, L Simpson, A Singleton, NL Smith, U Sovio, A Swift, H Syddall, AC Syvanen, T Tanaka, B Thorand, J Tichet, A Tonjes, T Tuomi, André Uitterlinden, KW van Dijk, Mandy van Hoek, D Varma, S Visvikis-Siest, V Vitart, N Vogelzangs, G Waeber, PJ Wagner, A Walley, GB Walters, KL Ward, H Watkins, MN Weedon, SH Wild, G Willemsen, JCM Witteman, JWG Yarnell, E Zeggini, D Zelenika, B Zethelius, GJ Zhai, JH Zhao, M.C. Zillikens, IB Borecki, RJF Loos, P Meneton, PKE Magnusson, DM Nathan, GH Williams, AT Hattersley, K Silander, V Salomaa, GD Smith, SR Bornstein, P Schwarz, J Spranger, F Karpe, AR Shuldiner, C Cooper, GV Dedoussis, M Serrano-Rios, AD Morris, L Lind, LJ Palmer, FB Hu, PW Franks, S Ebrahim, M Marmot, WHL Kao, JS Pankow, MJ Sampson, J Kuusisto, M Laakso, O Pedersen, PP Pramstaller, HE Wichmann, T Illig, I Rudan, AF Wright, M Stumvoll, H Campbell, JF Wilson, RN Bergman, TA Buchanan, FS Collins, KL Mohlke, J Tuomilehto, TT Valle, D Altshuler, JI Rotter, DS Siscovick, BWJH Penninx, DI Boomsma, P Deloukas, TD Spector, TM Frayling, L Ferrucci, A Kong, U Thorsteinsdottir, K Stefansson, Cornelia Duijn, YS Aulchenko, A Cao, A Scuteri, D Schlessinger, M Uda, A Ruokonen, MR Jarvelin, DM Waterworth, P Vollenweider, L Peltonen, V Mooser, GR Abecasis, NJ Wareham, R Sladek, P Froguel, RM Watanabe, JB Meigs, L Groop, M Boehnke, MI McCarthy, JC Florez, I Barroso, T Hansen

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

1821 Citations (Scopus)

Abstract

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Original language	Undefined/Unknown
Pages (from-to)	105-U32
Journal	Nature Genetics
Volume	42
Issue number	2
DOIs	https://doi.org/10.1038/ng.520
Publication status	Published - 2010

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EMC COEUR-09
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Access to Document

10.1038/ng.520

http://hdl.handle.net/1765/28243

Cite this

Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, AU., Wheeler, E., Glazer, NL., Bouatia-Naji, N., Gloyn, AL., Lindgren, CM., Magi, R., Morris, AP., Randall, J., Johnson, T., Elliott, P., Rybin, D., Thorleifsson, G., Steinthorsdottir, V., ... Hansen, T. (2010). New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature Genetics, 42(2), 105-U32. https://doi.org/10.1038/ng.520

@article{1b03afc0db87468693b9ed43da83097e,

title = "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk",

abstract = "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.",

author = "J Dupuis and C Langenberg and I Prokopenko and R Saxena and N Soranzo and AU Jackson and E Wheeler and NL Glazer and N Bouatia-Naji and AL Gloyn and CM Lindgren and R Magi and AP Morris and J Randall and T Johnson and P Elliott and D Rybin and G Thorleifsson and V Steinthorsdottir and Peter Henneman and H Grallert and Abbas Dehghan and Hottenga, {JJ (Jouke Jan)} and CS Franklin and P Navarro and K Song and A Goel and JRB Perry and JM Egan and T Lajunen and N Grarup and T Sparso and A Doney and BF Voight and HM Stringham and M Li and S Kanoni and P Shrader and C Cavalcanti-Proenca and M Kumari and L Qi and NJ Timpson and C Gieger and C Zabena and G Rocheleau and E Ingelsson and P An and J O'Connell and J Luan and A Elliott and SA McCarroll and F Payne and RM Roccasecca and F Pattou and P Sethupathy and K Ardlie and Ariyurek, {Y (Yavuz)} and B Balkau and P Barter and JP Beilby and Y Ben-Shlomo and R Benediktsson and AJ Bennett and S Bergmann and M Bochud and E Boerwinkle and A Bonnefond and LL Bonnycastle and K Borch-Johnsen and Y Bottcher and E Brunner and SJ Bumpstead and G Charpentier and YDI Chen and P Chines and R Clarke and LJM Coin and MN Cooper and M Cornelis and G Crawford and L Crisponi and INM Day and {de Geus}, EJC and J Delplanque and C Dina and MR Erdos and AC Fedson and A Fischer-Rosinsky and NG Forouhi and CS Fox and R Frants and MG Franzosi and P Galan and MO Goodarzi and J Graessler and CJ Groves and S Grundy and R Gwilliam and U Gyllensten and S Hadjadj and G Hallmans and N Hammond and XJ Han and AL Hartikainen and N Hassanali and C Hayward and SC Heath and S Hercberg and Cindy Herder and AA Hicks and DR Hillman and AD Hingorani and Bert Hofman and J Hui and J Hung and B Isomaa and PRV Johnson and T Jorgensen and A Jula and M Kaakinen and J Kaprio and YA Kesaniemi and M Kivimaki and B Knight and S Koskinen and P Kovacs and KO Kyvik and GM Lathrop and DA Lawlor and {Le Bacquer}, O and C Lecoeur and Yunlei Li and V Lyssenko and R Mahley and M Mangino and AK Manning and MT Martinez-Larrad and JB McAteer and LJ McCulloch and R McPherson and C Meisinger and D Melzer and D Meyre and BD Mitchell and MA Morken and S Mukherjee and S Naitza and N Narisu and MJ Neville and Ben Oostra and M Orru and R Pakyz and CNA Palmer and G Paolisso and C Pattaro and D Pearson and JF Peden and NL Pedersen and M Perola and AFH Pfeiffer and I Pichler and O Polasek and D Posthuma and SC Potter and A Pouta and MA Province and BM Psaty and W Rathmann and NW Rayner and K Rice and S Ripatti and Fernando Rivadeneira and M Roden and O Rolandsson and A Sandbaek and M Sandhu and S Sanna and AA Sayer and P Scheet and LJ Scott and U Seedorf and SJ Sharp and B Shields and G Sigurosson and E.J.G. Sijbrands and A Silveira and L Simpson and A Singleton and NL Smith and U Sovio and A Swift and H Syddall and AC Syvanen and T Tanaka and B Thorand and J Tichet and A Tonjes and T Tuomi and Andr{\'e} Uitterlinden and {van Dijk}, KW and {van Hoek}, Mandy and D Varma and S Visvikis-Siest and V Vitart and N Vogelzangs and G Waeber and PJ Wagner and A Walley and GB Walters and KL Ward and H Watkins and MN Weedon and SH Wild and G Willemsen and JCM Witteman and JWG Yarnell and E Zeggini and D Zelenika and B Zethelius and GJ Zhai and JH Zhao and M.C. Zillikens and IB Borecki and RJF Loos and P Meneton and PKE Magnusson and DM Nathan and GH Williams and AT Hattersley and K Silander and V Salomaa and GD Smith and SR Bornstein and P Schwarz and J Spranger and F Karpe and AR Shuldiner and C Cooper and GV Dedoussis and M Serrano-Rios and AD Morris and L Lind and LJ Palmer and FB Hu and PW Franks and S Ebrahim and M Marmot and WHL Kao and JS Pankow and MJ Sampson and J Kuusisto and M Laakso and O Pedersen and PP Pramstaller and HE Wichmann and T Illig and I Rudan and AF Wright and M Stumvoll and H Campbell and JF Wilson and RN Bergman and TA Buchanan and FS Collins and KL Mohlke and J Tuomilehto and TT Valle and D Altshuler and JI Rotter and DS Siscovick and BWJH Penninx and DI Boomsma and P Deloukas and TD Spector and TM Frayling and L Ferrucci and A Kong and U Thorsteinsdottir and K Stefansson and Cornelia Duijn and YS Aulchenko and A Cao and A Scuteri and D Schlessinger and M Uda and A Ruokonen and MR Jarvelin and DM Waterworth and P Vollenweider and L Peltonen and V Mooser and GR Abecasis and NJ Wareham and R Sladek and P Froguel and RM Watanabe and JB Meigs and L Groop and M Boehnke and MI McCarthy and JC Florez and I Barroso and T Hansen",

year = "2010",

doi = "10.1038/ng.520",

language = "Undefined/Unknown",

volume = "42",

pages = "105--U32",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "2",

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Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Magi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparso, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proenca, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Bottcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, YDI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, de Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, XJ, Hartikainen, AL, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, B, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jorgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martinez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, B, Orru, M, Pakyz, R, Palmer, CNA, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigurosson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvanen, AC, Tanaka, T, Thorand, B, Tichet, J, Tonjes, A, Tuomi, T, Uitterlinden, A, van Dijk, KW, van Hoek, M, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, GJ, Zhao, JH, Zillikens, MC, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Rios, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H, Wilson, JF, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, Duijn, C, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, MR, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC, Barroso, I & Hansen, T 2010, 'New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk', Nature Genetics, vol. 42, no. 2, pp. 105-U32. https://doi.org/10.1038/ng.520

TY - JOUR

T1 - New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

AU - Dupuis, J

AU - Langenberg, C

AU - Prokopenko, I

AU - Saxena, R

AU - Soranzo, N

AU - Jackson, AU

AU - Wheeler, E

AU - Glazer, NL

AU - Bouatia-Naji, N

AU - Gloyn, AL

AU - Lindgren, CM

AU - Magi, R

AU - Morris, AP

AU - Randall, J

AU - Johnson, T

AU - Elliott, P

AU - Rybin, D

AU - Thorleifsson, G

AU - Steinthorsdottir, V

AU - Henneman, Peter

AU - Grallert, H

AU - Dehghan, Abbas

AU - Hottenga, JJ (Jouke Jan)

AU - Franklin, CS

AU - Navarro, P

AU - Song, K

AU - Goel, A

AU - Perry, JRB

AU - Egan, JM

AU - Lajunen, T

AU - Grarup, N

AU - Sparso, T

AU - Doney, A

AU - Voight, BF

AU - Stringham, HM

AU - Li, M

AU - Kanoni, S

AU - Shrader, P

AU - Cavalcanti-Proenca, C

AU - Kumari, M

AU - Qi, L

AU - Timpson, NJ

AU - Gieger, C

AU - Zabena, C

AU - Rocheleau, G

AU - Ingelsson, E

AU - An, P

AU - O'Connell, J

AU - Luan, J

AU - Elliott, A

AU - McCarroll, SA

AU - Payne, F

AU - Roccasecca, RM

AU - Pattou, F

AU - Sethupathy, P

AU - Ardlie, K

AU - Ariyurek, Y (Yavuz)

AU - Balkau, B

AU - Barter, P

AU - Beilby, JP

AU - Ben-Shlomo, Y

AU - Benediktsson, R

AU - Bennett, AJ

AU - Bergmann, S

AU - Bochud, M

AU - Boerwinkle, E

AU - Bonnefond, A

AU - Bonnycastle, LL

AU - Borch-Johnsen, K

AU - Bottcher, Y

AU - Brunner, E

AU - Bumpstead, SJ

AU - Charpentier, G

AU - Chen, YDI

AU - Chines, P

AU - Clarke, R

AU - Coin, LJM

AU - Cooper, MN

AU - Cornelis, M

AU - Crawford, G

AU - Crisponi, L

AU - Day, INM

AU - de Geus, EJC

AU - Delplanque, J

AU - Dina, C

AU - Erdos, MR

AU - Fedson, AC

AU - Fischer-Rosinsky, A

AU - Forouhi, NG

AU - Fox, CS

AU - Frants, R

AU - Franzosi, MG

AU - Galan, P

AU - Goodarzi, MO

AU - Graessler, J

AU - Groves, CJ

AU - Grundy, S

AU - Gwilliam, R

AU - Gyllensten, U

AU - Hadjadj, S

AU - Hallmans, G

AU - Hammond, N

AU - Han, XJ

AU - Hartikainen, AL

AU - Hassanali, N

AU - Hayward, C

AU - Heath, SC

AU - Hercberg, S

AU - Herder, Cindy

AU - Hicks, AA

AU - Hillman, DR

AU - Hingorani, AD

AU - Hofman, Bert

AU - Hui, J

AU - Hung, J

AU - Isomaa, B

AU - Johnson, PRV

AU - Jorgensen, T

AU - Jula, A

AU - Kaakinen, M

AU - Kaprio, J

AU - Kesaniemi, YA

AU - Kivimaki, M

AU - Knight, B

AU - Koskinen, S

AU - Kovacs, P

AU - Kyvik, KO

AU - Lathrop, GM

AU - Lawlor, DA

AU - Le Bacquer, O

AU - Lecoeur, C

AU - Li, Yunlei

AU - Lyssenko, V

AU - Mahley, R

AU - Mangino, M

AU - Manning, AK

AU - Martinez-Larrad, MT

AU - McAteer, JB

AU - McCulloch, LJ

AU - McPherson, R

AU - Meisinger, C

AU - Melzer, D

AU - Meyre, D

AU - Mitchell, BD

AU - Morken, MA

AU - Mukherjee, S

AU - Naitza, S

AU - Narisu, N

AU - Neville, MJ

AU - Oostra, Ben

AU - Orru, M

AU - Pakyz, R

AU - Palmer, CNA

AU - Paolisso, G

AU - Pattaro, C

AU - Pearson, D

AU - Peden, JF

AU - Pedersen, NL

AU - Perola, M

AU - Pfeiffer, AFH

AU - Pichler, I

AU - Polasek, O

AU - Posthuma, D

AU - Potter, SC

AU - Pouta, A

AU - Province, MA

AU - Psaty, BM

AU - Rathmann, W

AU - Rayner, NW

AU - Rice, K

AU - Ripatti, S

AU - Rivadeneira, Fernando

AU - Roden, M

AU - Rolandsson, O

AU - Sandbaek, A

AU - Sandhu, M

AU - Sanna, S

AU - Sayer, AA

AU - Scheet, P

AU - Scott, LJ

AU - Seedorf, U

AU - Sharp, SJ

AU - Shields, B

AU - Sigurosson, G

AU - Sijbrands, E.J.G.

AU - Silveira, A

AU - Simpson, L

AU - Singleton, A

AU - Smith, NL

AU - Sovio, U

AU - Swift, A

AU - Syddall, H

AU - Syvanen, AC

AU - Tanaka, T

AU - Thorand, B

AU - Tichet, J

AU - Tonjes, A

AU - Tuomi, T

AU - Uitterlinden, André

AU - van Dijk, KW

AU - van Hoek, Mandy

AU - Varma, D

AU - Visvikis-Siest, S

AU - Vitart, V

AU - Vogelzangs, N

AU - Waeber, G

AU - Wagner, PJ

AU - Walley, A

AU - Walters, GB

AU - Ward, KL

AU - Watkins, H

AU - Weedon, MN

AU - Wild, SH

AU - Willemsen, G

AU - Witteman, JCM

AU - Yarnell, JWG

AU - Zeggini, E

AU - Zelenika, D

AU - Zethelius, B

AU - Zhai, GJ

AU - Zhao, JH

AU - Zillikens, M.C.

AU - Borecki, IB

AU - Loos, RJF

AU - Meneton, P

AU - Magnusson, PKE

AU - Nathan, DM

AU - Williams, GH

AU - Hattersley, AT

AU - Silander, K

AU - Salomaa, V

AU - Smith, GD

AU - Bornstein, SR

AU - Schwarz, P

AU - Spranger, J

AU - Karpe, F

AU - Shuldiner, AR

AU - Cooper, C

AU - Dedoussis, GV

AU - Serrano-Rios, M

AU - Morris, AD

AU - Lind, L

AU - Palmer, LJ

AU - Hu, FB

AU - Franks, PW

AU - Ebrahim, S

AU - Marmot, M

AU - Kao, WHL

AU - Pankow, JS

AU - Sampson, MJ

AU - Kuusisto, J

AU - Laakso, M

AU - Pedersen, O

AU - Pramstaller, PP

AU - Wichmann, HE

AU - Illig, T

AU - Rudan, I

AU - Wright, AF

AU - Stumvoll, M

AU - Campbell, H

AU - Wilson, JF

AU - Bergman, RN

AU - Buchanan, TA

AU - Collins, FS

AU - Mohlke, KL

AU - Tuomilehto, J

AU - Valle, TT

AU - Altshuler, D

AU - Rotter, JI

AU - Siscovick, DS

AU - Penninx, BWJH

AU - Boomsma, DI

AU - Deloukas, P

AU - Spector, TD

AU - Frayling, TM

AU - Ferrucci, L

AU - Kong, A

AU - Thorsteinsdottir, U

AU - Stefansson, K

AU - Duijn, Cornelia

AU - Aulchenko, YS

AU - Cao, A

AU - Scuteri, A

AU - Schlessinger, D

AU - Uda, M

AU - Ruokonen, A

AU - Jarvelin, MR

AU - Waterworth, DM

AU - Vollenweider, P

AU - Peltonen, L

AU - Mooser, V

AU - Abecasis, GR

AU - Wareham, NJ

AU - Sladek, R

AU - Froguel, P

AU - Watanabe, RM

AU - Meigs, JB

AU - Groop, L

AU - Boehnke, M

AU - McCarthy, MI

AU - Florez, JC

AU - Barroso, I

AU - Hansen, T

PY - 2010

Y1 - 2010

N2 - Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

AB - Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

U2 - 10.1038/ng.520

DO - 10.1038/ng.520

M3 - Article

C2 - 20081858

SN - 1061-4036

VL - 42

SP - 105-U32

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -