Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
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.
Zeggini
Eleftheria
E
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.
Weedon
Michael N
MN
Lindgren
Cecilia M
CM
Frayling
Timothy M
TM
Elliott
Katherine S
KS
Lango
Hana
H
Timpson
Nicholas J
NJ
Perry
John R B
JR
Rayner
Nigel W
NW
Freathy
Rachel M
RM
Barrett
Jeffrey C
JC
Shields
Beverley
B
Morris
Andrew P
AP
Ellard
Sian
S
Groves
Christopher J
CJ
Harries
Lorna W
LW
Marchini
Jonathan L
JL
Owen
Katharine R
KR
Knight
Beatrice
B
Cardon
Lon R
LR
Walker
Mark
M
Hitman
Graham A
GA
Morris
Andrew D
AD
Doney
Alex S F
AS
McCarthy
Mark I
MI
Hattersley
Andrew T
AT
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
C078492:HHEX protein, human; D018398:Homeodomain Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D014157:Transcription Factors