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New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
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2010 (English)In: Nature Genetics, ISSN 1061-4036, Vol. 42, no 2, 105-116 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 42, no 2, 105-116 p.
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Medical and Health Sciences
URN: urn:nbn:se:uu:diva-122989DOI: 10.1038/ng.520ISI: 000274084400005PubMedID: 20081858OAI: oai:DiVA.org:uu-122989DiVA: diva2:311571
Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2011-05-17Bibliographically approved

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GeriatricsDepartment of Immunology, Genetics and PathologyDepartment of Medical Sciences
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