TY - JOUR
T1 - A genome-wide association study identifies novel risk loci for type 2 diabetes
AU - Sladek, Robert
AU - Rocheleau, Ghislain
AU - Rung, Johan
AU - Dina, Christian
AU - Shen, Lishuang
AU - Serre, David
AU - Boutin, Philippe
AU - Vincent, Daniel
AU - Belisle, Alexandre
AU - Hadjadj, Samy
AU - Balkau, Beverley
AU - Heude, Barbara
AU - Charpentier, Guillaume
AU - Hudson, Thomas J.
AU - Montpetit, Alexandre
AU - Pshezhetsky, Alexey V.
AU - Prentki, Marc
AU - Posner, Barry I.
AU - Balding, David J.
AU - Meyre, David
AU - Polychronakos, Constantin
AU - Froguel, Philippe
N1 - Funding Information:
Acknowledgements This work was funded by Genome Canada, Génome Québec, and the Canada Foundation for Innovation. Cohort recruitment was supported by the Association Franc¸aise des Diabétiques, INSERM, CNAMTS, Centre Hospitalier Universitaire Poitiers, La Fondation de France and industrial partners. We thank all individuals who participated as cases or controls in this study. C. Petit, J-P. Riveline and S. Franc were instrumental in recruitment and S. Brunet, F. Bacot, R. Frechette, V. Catudal, M. Deweirder, F. Allegaert, P. Laflamme, P. Lepage, W. Astle, M. Leboeuf and S. Leroux provided technical assistance. K. Shazand and N. Foisset provided organizational guidance. Large-scale computations were made possible by the CLUMEQ supercomputer facility.
PY - 2007/2/22
Y1 - 2007/2/22
N2 - 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 β-cells, and two linkage disequilibrium blocks that contain genes potentially involved in β-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.
AB - 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 β-cells, and two linkage disequilibrium blocks that contain genes potentially involved in β-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.
UR - http://www.scopus.com/inward/record.url?scp=33847176604&partnerID=8YFLogxK
U2 - 10.1038/nature05616
DO - 10.1038/nature05616
M3 - Article
C2 - 17293876
AN - SCOPUS:33847176604
SN - 0028-0836
VL - 445
SP - 881
EP - 885
JO - Nature
JF - Nature
IS - 7130
ER -