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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

Nature genetics

Publication Date

07/2010

Volume

42

Pages

579 - 589

Addresses

Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.

Keywords

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