Year: 2020
Type: article
Abstract: To identify novel genetic loci associated with fasting glucose concentrations, we examined the leading association signals in 10 genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding the 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 thirteen case-control studies totalling 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.
DOI: 10.17615/zy0z-zw04
Authors: Jackson, Anne U, Saxena, Richa, de Geus, Eco J C, Bergman, Richard N, Aulchenko, Yurii, Bochud, Murielle, Cao, Antonio, Soranzo, Nicole, Beckmann, Jacques S, Thorleifsson, Gudmar, Crisponi, Laura, Coin, Lachlan, Prokopenko, Inga, Dehghan, Abbas, Chen, Wei-Min, Manning, Alisa K, Wheeler, Eleanor, Langenberg, Claudia, Deloukas, Panos, Buchanan, Thomas A, Loos, Ruth J F, Sanna, Serena, Kaakinen, Marika, Ahmadi, Kourosh, Bonnycastle, Lori L, Erdos, Michael R, Lyssenko, Valeriya, Collins, Francis S, Florez, Jose C, Cervino, Alessandra, Hottenga, Jouke-Jan, Potter, Simon C
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: American Diabetes Association, GlaxoSmithKline, Health Services Research and Development, Wellcome Trust, European Bioinformatics Institute, National Institute for Health and Care Research, Diabetes UK, European Commission, ZonMw, Bundesministerium für Bildung und Forschung, Bundesministerium für Gesundheit, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Vetenskapsrådet, Diabetestutkimussäätiö, National Institutes of Health, Medical Research Council, National Institute on Aging
Awards: G1077033501, G1140801657, G1409398652, G1558193350, G178382592, G2139896254, G2238725043, G2531204615, G2563633029, G2563833389, G2918387404, G3367174484, G3814398992, G4599390081, European Network for Genetic and Genomic Epidemiology, G6091493096, G6728033037, G70080636, G822877548, G836522160, The genetics of weight, BMI, adiposity and obesity, G961365294
OpenAlex ID: W4299726409