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.

Original publication

DOI

10.1038/ng.609

Type

Journal article

Journal

Nat Genet

Publication Date

07/2010

Volume

42

Pages

579 - 589

Keywords

Blood Glucose, Diabetes Mellitus, Type 2, Dual-Specificity Phosphatases, Fasting, Gene Dosage, Gene Expression Profiling, Genetic Heterogeneity, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Hepatocyte Nuclear Factor 1-alpha, Humans, KCNQ1 Potassium Channel, Meta-Analysis as Topic, Mitogen-Activated Protein Kinase Phosphatases, Polymorphism, Single Nucleotide