Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.

Journal article

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

Authors: Morris, A; Voight, B; Teslovich, T; Ferreira, T; Segrè, A

• Publication status: Published
• Journal: Nature genetics
• Volume: 44
• Issue: 9
• Pages: 981-990
• Publication date: 2012-09-01
• DOI: 10.1038/ng.2383
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Genetic Investigation of ANthropometric Traits (GIANT) Consortium; Linkage Disequilibrium; Sex Factors; Diabetes Mellitus, Type 2; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; Case-Control Studies; Wellcome Trust Case Control Consortium; Humans; Genes; Asian Genetic Epidemiology Network–Type 2 Diabetes (AGEN-T2D) Consortium; Pakistan; Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Male; Female; South Asian Type 2 Diabetes (SAT2D) Consortium