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Variants in MTNR1B influence fasting glucose levels.
Nat. Genet. 41, 77-81 (2009)
To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
genome-wide association; beta-cell function; gene-expression; plasma-glucose; risk loci; melatonin; triglyceride; replication; haplotype; impact
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
Zeitschrift
Nature Genetics
Quellenangaben
Band: 41,
Heft: 1,
Seiten: 77-81
Verlag
Nature Publishing Group
Verlagsort
New York, NY
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)