Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.

Journal article

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: Voight, B; Scott, L; Steinthorsdottir, V; Morris, A; Dina, C

• Journal: Nature genetics
• Volume: 42
• Issue: 7
• Pages: 579-589
• Publication date: 2010-07-01
• DOI: 10.1038/ng.609
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Fasting; Mitogen-Activated Protein Kinase Phosphatases; Diabetes Mellitus, Type 2; Blood Glucose; Gene Expression Profiling; MAGIC investigators; Genome-Wide Association Study; Gene Dosage; Humans; Genetic Heterogeneity; Genetic Predisposition to Disease; Hepatocyte Nuclear Factor 1-alpha; KCNQ1 Potassium Channel; Genome, Human; Dual-Specificity Phosphatases; Meta-Analysis as Topic; Polymorphism, Single Nucleotide; GIANT Consortium