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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.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20081858","pmcid":"PMC3018764","openalex_id":null,"authors":[],"funders":[{"funder_name":"Medical Research Council","grant_id":"G0600705","title":"Centre for molecular-based causal analyses in health and disease"},{"funder_name":"Medical Research Council","grant_id":"MC_U127561128","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UP_A620_1015","title":null},{"funder_name":"Wellcome Trust","grant_id":"077011","title":null},{"funder_name":"Chief Scientist Office","grant_id":"CZB/4/710","title":null},{"funder_name":"Medical 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