Variants in MTNR1B influence fasting glucose levels

By I. Prokopenko, C. Langenberg, Jose C. Florez, J. Florez, R. Saxena, R. Saxena, N. Soranzo, G. Thorleifsson, Ruth J. F. Loos, Alisa K Manning and 107 more. Nature Genetics, 2008

723 citations recorded by the source corpus.

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 × 10−50) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 × 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 × 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 × 10−57) and GCK (rs4607517, P = 1.0 × 10−25) loci.

Subfields: Endocrine and Autonomic Systems, Endocrinology, Diabetes and Metabolism, Genetics

View Paper: https://www.semanticscholar.org/paper/a75a7cf36b7d067bc35a5351447c04bc6f8ecd36

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In Endocrine and Autonomic Systems

In Endocrinology, Diabetes and Metabolism

John P. A. Ioannidis

In Genetics

Citations in the corpus

Genotype Imputation (2009, neutral): “In this way, it has been possible to contrast results from genetic studies of blood lipid levels (111) with those of previous studies of coronary artery disease (105), to compare results of studies of blood glucose levels in nondiabetic individuals (79) with those of previous case-control studies of”
International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors (2010, background): “sons with genetic variations in the MTNR1B gene encoding the MT2 melatonin receptor (Bouatia-Naji et al., 2009; Lyssenko et al., 2009; Prokopenko et al., 2009).”
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Replication in genome-wide association studies (2009, background): “Prospective metaanalyses for height, BMI and fasting glucose have dealt with the issue of phenotype harmonization in a trait-by-trait basis [37, 43, 53, 67].”
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SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome (2011, neutral): “, 2010), diabetes (Dupuis et al., 2010; Prokopenko et al., 2009), or cholesterol and lipid metabolism (Musunuru et al.”
METAL: fast and efficient meta-analysis of genomewide association scans (2010, methodology): “Availability and implementation: METAL, including source code, documentation, examples, and executables, is available at http:// www.sph.umich.edu/csg/abecasis/metal/ Contact: goncalo@umich.edu Received on April 15, 2010; revised on June 17, 2010; accepted on June 18, 2010”