title: Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
abstract: 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.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Elliott
authors.forename: Hana
authors.initials: H
authors.lastname: Lango
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: John R B
authors.initials: JR
authors.lastname: Perry
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Rayner
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Barrett
authors.forename: Beverley
authors.initials: B
authors.lastname: Shields
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Groves
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Marchini
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Owen
authors.forename: Beatrice
authors.initials: B
authors.lastname: Knight
authors.forename: Lon R
authors.initials: LR
authors.lastname: Cardon
authors.forename: Mark
authors.initials: M
authors.lastname: Walker
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hitman
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Morris
authors.forename: Alex S F
authors.initials: AS
authors.lastname: Doney
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007438:Introns; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics; D006113:United Kingdom
chemical_list: C078492:HHEX protein, human; D018398:Homeodomain Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D014157:Transcription Factors