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

Josée Dupuis ; Claudia Langenberg ; Inga Prokopenko ; Richa Saxena ; Nicole Soranzo ; Anne U Jackson ; Eleanor Wheeler ; Nicole L Glazer ; Nabila Bouatia-Naji ; Anna L Gloyn ; +298 more... 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Peter Schwarz ; Joachim Spranger ; Fredrik Karpe ; Alan R Shuldiner ; Cyrus Cooper ; George V Dedoussis ; Manuel Serrano-Ríos ; Andrew D Morris ; Lars Lind ; Lyle J Palmer ; Frank B Hu ; Paul W Franks ; Shah Ebrahim ; Michael Marmot ; WH Linda Kao ; James S Pankow ; Michael J Sampson ; Johanna Kuusisto ; Markku Laakso ; Torben Hansen ; Oluf Pedersen ; Peter Paul Pramstaller ; H Erich Wichmann ; Thomas Illig ; Igor Rudan ; Alan F Wright ; Michael Stumvoll ; Harry Campbell ; James F Wilson ; Anders Hamsten on behalf of Procardis Consortium ; MAGIC investigators ; Richard N Bergman ; Thomas A Buchanan ; Francis S Collins ; Karen L Mohlke ; Jaakko Tuomilehto ; Timo T Valle ; David Altshuler ; Jerome I Rotter ; David S Siscovick ; Brenda WJH Penninx ; Dorret I Boomsma ; Panos Deloukas ; Timothy D Spector ; Timothy M Frayling ; Luigi Ferrucci ; Augustine Kong ; Unnur Thorsteinsdottir ; Kari Stefansson ; Cornelia M van Duijn ; Yurii S Aulchenko ; Antonio Cao ; Angelo Scuteri ; David Schlessinger ; Manuela Uda ; Aimo Ruokonen ; Marjo-Riitta Jarvelin ; Dawn M Waterworth ; Peter Vollenweider ; Leena Peltonen ; Vincent Mooser ; Goncalo R Abecasis ; Nicholas J Wareham ; Robert Sladek ; Philippe Froguel ; Richard M Watanabe ; James B Meigs ; Leif Groop ; Michael Boehnke ; Mark I McCarthy ; Jose C Florez ; Inês Barroso ; (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature genetics, 42 (2). pp. 105-116. ISSN 1061-4036 DOI: 10.1038/ng.520
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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.
Item Type Article
ISI 274084400005
Date Deposited 17 Oct 2011 14:48

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