We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
- Authors
Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga; Saxena, Richa; Soranzo, Nicole; Jackson, Anne U.; Wheeler, Eleanor; Glazer, Nicole L.; Bouatia-Naji, Nabila; Gloyn, Anna L.; Lindgren, Cecilia M.; Mägi, Reedik; Morris, Andrew P.; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Henneman, Peter
- 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.
- Subjects
TYPE 2 diabetes; GLUCOSE; PANCREATIC beta cells; INSULIN; CELL proliferation; GENOMICS; DIABETES
- Publication
Nature Genetics, 2010, Vol 42, Issue 2, p105
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.520