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

Dupuis, J.; Langenberg, C.; Prokopenko, I.; Saxena, R.; Soranzo, N.; Jackson, A.U.; Wheeler, E.; Glazer, N.L.; Bouatia-Naji, N.; Gloyn, A.L.; Lindgren, C.M.; Mägi, R.; Morris, A.P.; Randall, J.; Johnson, T.; Elliott, P.; Rybin, D.; Thorleifsson, G.; Steinthorsdottir, V.; Henneman, P.; Grallert, H.; Dehghan, A.; Hottenga, J.J.; Franklin, C.S.; Navarro, P.; Song, K.; Goel, A.; Perry, J.R.; Egan, J.M.; Lajunen, T.; Grarup, N.; Sparsø, T.; Doney, A.; Voight, B.F.; Stringham, H.M.; Li, M.; Kanoni, S.; Shrader, P.; Cavalcanti-Proença, C.; Kumari, M.; Qi, L.; Timpson, N.J.; Gieger, C.; Zabena, C.; Rocheleau, G.; Ingelsson, E.; An, P.; O'Connell, J.; Luan, J.; Elliott, A.; McCarroll, S.A.; Payne, F.; Roccasecca, R.M.; Pattou, F.; Sethupathy, P.; Ardlie, K.; Ariyurek, Y.; Balkau, B.; Barter, P.; Beilby, J.P.; Ben-Shlomo, Y.; Benediktsson, R.; Bennett, A.J.; Bergmann, S.; Bochud, M.; Boerwinkle, E.; Bonnefond, A.; Bonnycastle, L.L.; Borch-Johnsen, K.; Böttcher, Y.; Brunner, E.; Bumpstead, S.J.; Charpentier, G.; Chen, Y.D.; Chines, P.; Clarke, R.; Coin, L.J.; Cooper, M.N.; Cornelis, M.; Crawford, G.; Crisponi, L.; Day, I.N.; de Geus, E.J.; Delplanque, J.; Dina, C.; Erdos, M.R.; Fedson, A.C.; Fischer-Rosinsky, A.; Forouhi, N.G.; Fox, C.S.; Frants, R.; Franzosi, M.G.; Galan, P.; Goodarzi, M.O.; Graessler, J.; Groves, C.J.; Grundy, S.; Gwilliam, R.; Gyllensten, U.; Hadjadj, S.; Hallmans, G.; Hammond, N.; Han, X.; Hartikainen, A.L.; Hassanali, N.; Hayward, C.; Heath, S.C.; Hercberg, S.; Herder, C.; Hicks, A.A.; Hillman, D.R.; Hingorani, A.D.; Hofman, A.; Hui, J.; Hung, J.; Isomaa, B.; Johnson, P.R.; Jørgensen, T.; Jula, A.; Kaakinen, M.; Kaprio, J.; Kesaniemi, Y.A.; Kivimaki, M.; Knight, B.; Koskinen, S.; Kovacs, P.; Kyvik, K.O.; Lathrop, G.M.; Lawlor, D.A.; Le Bacquer, O.; Lecoeur, C.; Li, Y.; Lyssenko, V.; Mahley, R.; Mangino, M.; Manning, A.K.; Martínez-Larrad, M.T.; McAteer, J.B.; McCulloch, L.J.; McPherson, R.; Meisinger, C.; Melzer, D.; Meyre, D.; Mitchell, B.D.; Morken, M.A.; Mukherjee, S.; Naitza, S.; Narisu, N.; Neville, M.J.; Oostra, B.A.; Orrù, M.; Pakyz, R.; Palmer, C.N.; Paolisso, G.; Pattaro, C.; Pearson, D.; Peden, J.F.; Pedersen, N.L.; Perola, M.; Pfeiffer, A.F.; Pichler, I.; Polasek, O.; Posthuma, D.; Potter, S.C.; Pouta, A.; Province, M.A.; Psaty, B.M.; Rathmann, W.; Rayner, N.W.; Rice, K.; Ripatti, S.; Rivadeneira, F.; Roden, M.; Rolandsson, O.; Sandbaek, A.; Sandhu, M.; Sanna, S.; Sayer, A.A.; Scheet, P.; Scott, L.J.; Seedorf, U.; Sharp, S.J.; Shields, B.; Sigurethsson, G.; Sijbrands, E.J.; Silveira, A.; Simpson, L.; Singleton, A.; Smith, N.L.; Sovio, U.; Swift, A.; Syddall, H.; Syvänen, A.C.; Tanaka, T.; Thorand, B.; Tichet, J.; Tönjes, A.; Tuomi, T.; Uitterlinden, A.G.; van Dijk, K.W.; van Hoek, M.; Varma, D.; Visvikis-Siest, S.; Vitart, V.; Vogelzangs, N.; Waeber, G.; Wagner, P.J.; Walley, A.; Walters, G.B.; Ward, K.L.; Watkins, H.; Weedon, M.N.; Wild, S.H.; Willemsen, G.; Witteman, J.C.; Yarnell, J.W.; Zeggini, E.; Zelenika, D.; Zethelius, B.; Zhai, G.; Zhao, J.H.; Zillikens, M.C.; Borecki, I.B.; Loos, R.J.; Meneton, P.; Magnusson, P.K.; Nathan, D.M.; Williams, G.H.; Hattersley, A.T.; Silander, K.; Salomaa, V.; Smith, G.D.; Bornstein, S.R.; Schwarz, P.; Spranger, J.; Karpe, F.; Shuldiner, A.R.; Cooper, C.; Dedoussis, G.V.; Serrano-Ríos, M.; Morris, A.D.; Lind, L.; Palmer, L.J.; Hu, F.B.; Franks, P.W.; Ebrahim, S.; Marmot, M.; Kao, W.H.; Pankow, J.S.; Sampson, M.J.; Kuusisto, J.; Laakso, M.; Hansen, T.; Pedersen, O.; Pramstaller, P.P.; Wichmann, H.E.; Illig, T.; Rudan, I.; Wright, A.F.; Stumvoll, M.; Campbell, H.; Wilson, J.F.; Bergman, R.N.; Buchanan, T.A.; Collins, F.S.; Mohlke, K.L.; Tuomilehto, J.; Valle, T.T.; Altshuler, D.; Rotter, J.I.; Siscovick, D.S.; Penninx, B.W.; Boomsma, D.I.; Deloukas, P.; Spector, T.D.; Frayling, T.M.; Ferrucci, L.; Kong, A.; Thorsteinsdottir, U.; Stefansson, K.; van Duijn, C.M.; Aulchenko, Y.S.; Cao, A.; Scuteri, A.; Schlessinger, D.; Uda, M.; Ruokonen, A.; Jarvelin, M.R.; Waterworth, D.M.; Vollenweider, P.; Peltonen, L.; Mooser, V.; Abecasis, G.R.; Wareham, N.J.; Sladek, R.; Froguel, P.; Watanabe, R.M.; Meigs, J.B.; Groop, L.; Boehnke, M.; McCarthy, M.I.; Florez, J.C.; Barroso, I.

doi:10.1038/ng.520

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

Details

Download: 20081858_BIB_68555FB264D9.pdf (1125.27 [Ko])
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Version: Author's accepted manuscript
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Serval ID

serval:BIB_68555FB264D9

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature genetics

Author(s)

Dupuis J., Langenberg C., Prokopenko I., Saxena R., Soranzo N., Jackson A.U., Wheeler E., Glazer N.L., Bouatia-Naji N., Gloyn A.L., Lindgren C.M., Mägi R., Morris A.P., Randall J., Johnson T., Elliott P., Rybin D., Thorleifsson G., Steinthorsdottir V., Henneman P., Grallert H., Dehghan A., Hottenga J.J., Franklin C.S., Navarro P., Song K., Goel A., Perry J.R., Egan J.M., Lajunen T., Grarup N., Sparsø T., Doney A., Voight B.F., Stringham H.M., Li M., Kanoni S., Shrader P., Cavalcanti-Proença C., Kumari M., Qi L., Timpson N.J., Gieger C., Zabena C., Rocheleau G., Ingelsson E., An P., O'Connell J., Luan J., Elliott A., McCarroll S.A., Payne F., Roccasecca R.M., Pattou F., Sethupathy P., Ardlie K., Ariyurek Y., Balkau B., Barter P., Beilby J.P., Ben-Shlomo Y., Benediktsson R., Bennett A.J., Bergmann S., Bochud M., Boerwinkle E., Bonnefond A., Bonnycastle L.L., Borch-Johnsen K., Böttcher Y., Brunner E., Bumpstead S.J., Charpentier G., Chen Y.D., Chines P., Clarke R., Coin L.J., Cooper M.N., Cornelis M., Crawford G., Crisponi L., Day I.N., de Geus E.J., Delplanque J., Dina C., Erdos M.R., Fedson A.C., Fischer-Rosinsky A., Forouhi N.G., Fox C.S., Frants R., Franzosi M.G., Galan P., Goodarzi M.O., Graessler J., Groves C.J., Grundy S., Gwilliam R., Gyllensten U., Hadjadj S., Hallmans G., Hammond N., Han X., Hartikainen A.L., Hassanali N., Hayward C., Heath S.C., Hercberg S., Herder C., Hicks A.A., Hillman D.R., Hingorani A.D., Hofman A., Hui J., Hung J., Isomaa B., Johnson P.R., Jørgensen T., Jula A., Kaakinen M., Kaprio J., Kesaniemi Y.A., Kivimaki M., Knight B., Koskinen S., Kovacs P., Kyvik K.O., Lathrop G.M., Lawlor D.A., Le Bacquer O., Lecoeur C., Li Y., Lyssenko V., Mahley R., Mangino M., Manning A.K., Martínez-Larrad M.T., McAteer J.B., McCulloch L.J., McPherson R., Meisinger C., Melzer D., Meyre D., Mitchell B.D., Morken M.A., Mukherjee S., Naitza S., Narisu N., Neville M.J., Oostra B.A., Orrù M., Pakyz R., Palmer C.N., Paolisso G., Pattaro C., Pearson D., Peden J.F., Pedersen N.L., Perola M., Pfeiffer A.F., Pichler I., Polasek O., Posthuma D., Potter S.C., Pouta A., Province M.A., Psaty B.M., Rathmann W., Rayner N.W., Rice K., Ripatti S., Rivadeneira F., Roden M., Rolandsson O., Sandbaek A., Sandhu M., Sanna S., Sayer A.A., Scheet P., Scott L.J., Seedorf U., Sharp S.J., Shields B., Sigurethsson G., Sijbrands E.J., Silveira A., Simpson L., Singleton A., Smith N.L., Sovio U., Swift A., Syddall H., Syvänen A.C., Tanaka T., Thorand B., Tichet J., Tönjes A., Tuomi T., Uitterlinden A.G., van Dijk K.W., van Hoek M., Varma D., Visvikis-Siest S., Vitart V., Vogelzangs N., Waeber G., Wagner P.J., Walley A., Walters G.B., Ward K.L., Watkins H., Weedon M.N., Wild S.H., Willemsen G., Witteman J.C., Yarnell J.W., Zeggini E., Zelenika D., Zethelius B., Zhai G., Zhao J.H., Zillikens M.C., Borecki I.B., Loos R.J., Meneton P., Magnusson P.K., Nathan D.M., Williams G.H., Hattersley A.T., Silander K., Salomaa V., Smith G.D., Bornstein S.R., Schwarz P., Spranger J., Karpe F., Shuldiner A.R., Cooper C., Dedoussis G.V., Serrano-Ríos M., Morris A.D., Lind L., Palmer L.J., Hu F.B., Franks P.W., Ebrahim S., Marmot M., Kao W.H., Pankow J.S., Sampson M.J., Kuusisto J., Laakso M., Hansen T., Pedersen O., Pramstaller P.P., Wichmann H.E., Illig T., Rudan I., Wright A.F., Stumvoll M., Campbell H., Wilson J.F., Bergman R.N., Buchanan T.A., Collins F.S., Mohlke K.L., Tuomilehto J., Valle T.T., Altshuler D., Rotter J.I., Siscovick D.S., Penninx B.W., Boomsma D.I., Deloukas P., Spector T.D., Frayling T.M., Ferrucci L., Kong A., Thorsteinsdottir U., Stefansson K., van Duijn C.M., Aulchenko Y.S., Cao A., Scuteri A., Schlessinger D., Uda M., Ruokonen A., Jarvelin M.R., Waterworth D.M., Vollenweider P., Peltonen L., Mooser V., Abecasis G.R., Wareham N.J., Sladek R., Froguel P., Watanabe R.M., Meigs J.B., Groop L., Boehnke M., McCarthy M.I., Florez J.C., Barroso I.

Working group(s)

DIAGRAM Consortium, GIANT Consortium, Global BPgen Consortium, Anders Hamsten on behalf of Procardis Consortium, MAGIC investigators

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

02/2010

Peer-reviewed

Oui

Volume

Number

Pages

105-116

Language

english

Notes

Publication types: Journal Article
Publication Status: ppublish

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.

Keywords

Adolescent, Adult, Alleles, Blood Glucose/genetics, Blood Glucose/metabolism, Child, DNA Copy Number Variations/genetics, Databases, Genetic, Diabetes Mellitus, Type 2/genetics, Fasting/blood, Gene Expression Regulation, Genetic Loci/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeostasis/genetics, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Quantitative Trait, Heritable, Reproducibility of Results

URN

urn:nbn:ch:serval-BIB_68555FB264D94

OAI-PMH

oai:serval.unil.ch:BIB_68555FB264D9

DOI

10.1038/ng.520

Pubmed

20081858

Web of science

000274084400005

Create date

25/01/2010 16:38