A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.
Scott
Laura J
LJ
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Mohlke
Karen L
KL
Bonnycastle
Lori L
LL
Willer
Cristen J
CJ
Li
Yun
Y
Duren
William L
WL
Erdos
Michael R
MR
Stringham
Heather M
HM
Chines
Peter S
PS
Jackson
Anne U
AU
Prokunina-Olsson
Ludmila
L
Ding
Chia-Jen
CJ
Swift
Amy J
AJ
Narisu
Narisu
N
Hu
Tianle
T
Pruim
Randall
R
Xiao
Rui
R
Li
Xiao-Yi
XY
Conneely
Karen N
KN
Riebow
Nancy L
NL
Sprau
Andrew G
AG
Tong
Maurine
M
White
Peggy P
PP
Hetrick
Kurt N
KN
Barnhart
Michael W
MW
Bark
Craig W
CW
Goldstein
Janet L
JL
Watkins
Lee
L
Xiang
Fang
F
Saramies
Jouko
J
Buchanan
Thomas A
TA
Watanabe
Richard M
RM
Valle
Timo T
TT
Kinnunen
Leena
L
Abecasis
Gonçalo R
GR
Pugh
Elizabeth W
EW
Doheny
Kimberly F
KF
Bergman
Richard N
RN
Tuomilehto
Jaakko
J
Collins
Francis S
FS
Boehnke
Michael
M
D016022:Case-Control Studies; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D021901:DNA, Intergenic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005387:Finland; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007438:Introns; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D021901:DNA, Intergenic; D018969:Insulin-Like Growth Factor Binding Proteins