A genome-wide association study identifies novel risk loci for type 2 diabetes.
Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,935 single-nucleotide polymorphisms in a French case-control cohort. Markers with the most significant difference in genotype frequencies between cases of type 2 diabetes and controls were fast-tracked for testing in a second cohort. This identified four loci containing variants that confer type 2 diabetes risk, in addition to confirming the known association with the TCF7L2 gene. These loci include a non-synonymous polymorphism in the zinc transporter SLC30A8, which is expressed exclusively in insulin-producing beta-cells, and two linkage disequilibrium blocks that contain genes potentially involved in beta-cell development or function (IDE-KIF11-HHEX and EXT2-ALX4). These associations explain a substantial portion of disease risk and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits.
Sladek
Robert
R
Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, Montreal H3A 1A4, Canada.
Rocheleau
Ghislain
G
Rung
Johan
J
Dina
Christian
C
Shen
Lishuang
L
Serre
David
D
Boutin
Philippe
P
Vincent
Daniel
D
Belisle
Alexandre
A
Hadjadj
Samy
S
Balkau
Beverley
B
Heude
Barbara
B
Charpentier
Guillaume
G
Hudson
Thomas J
TJ
Montpetit
Alexandre
A
Pshezhetsky
Alexey V
AV
Prentki
Marc
M
Posner
Barry I
BI
Balding
David J
DJ
Meyre
David
D
Polychronakos
Constantin
C
Froguel
Philippe
P
D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005602:France; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D015810:Linkage Disequilibrium; D000075703:Zinc Transporter 8
D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8