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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, AU; Wheeler, E; ... MAGIC Investigators, ; + view all (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. NAT GENET , 42 (2) 105 - U32. 10.1038/ng.520.

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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.

Type: Article
Title: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
DOI: 10.1038/ng.520
Keywords: GENOME-WIDE ASSOCIATION, BETA-CELL DYSFUNCTION, PLASMA-GLUCOSE, INSULIN-SECRETION, TRIGLYCERIDE LEVELS, ESSENTIAL COMPONENTS, MODEL ASSESSMENT, COMMON VARIANTS, CIRCADIAN CLOCK, DISEASE RISK
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: http://discovery.ucl.ac.uk/id/eprint/174642
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