The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.

Original publication

DOI

10.1126/science.1142364

Type

Journal article

Journal

Science (New York, N.Y.)

Publication Date

06/2007

Volume

316

Pages

1336 - 1341

Addresses

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.

Keywords

Wellcome Trust Case Control Consortium (WTCCC), Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Insulin-Like Growth Factor Binding Proteins, Homeodomain Proteins, Transcription Factors, Oligonucleotide Array Sequence Analysis, Case-Control Studies, Chromosome Mapping, Polymorphism, Single Nucleotide, Genes, p16, Genome, Human, Introns, Adult, Aged, Middle Aged, Female, Male, Meta-Analysis as Topic, United Kingdom