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.

Original publication

DOI

10.1038/ng.2383

Type

Journal article

Journal

Nature genetics

Publication Date

09/2012

Volume

44

Pages

981 - 990

Addresses

Wellcome Trust Centre for Human Genetics, University of Oxford, UK. amorris@well.ox.ac.uk

Keywords

Wellcome Trust Case Control Consortium, Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Asian Genetic Epidemiology Network–Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Case-Control Studies, Sex Factors, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Genes, Pakistan, Female, Male, Genome-Wide Association Study