Open Access Green as soon as Postprint is submitted to ZB.
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Nat. Genet. 42, 105-116 (2010)
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.
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide association; Beta-cell Dysdunction; Plasma-glucose; Insulin-secretion; Trigyceride levels; Essential compionents; Model assessment; Common variants; Circadian clock; Disease risk
ISSN (print) / ISBN 1061-4036
Journal Nature Genetics
Quellenangaben Volume: 42, Issue: 2, Pages: 105-116
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)