title: Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
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mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D005215:Fasting / Q000097:blood; D018628:Gene Dosage; D020869:Gene Expression Profiling; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D015201:Meta-Analysis as Topic; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D001786:Blood Glucose; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051657:KCNQ1 Potassium Channel; D054639:Mitogen-Activated Protein Kinase Phosphatases; C104821:DUSP9 protein, human; D054637:Dual-Specificity Phosphatases