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- Title
WFS1 Is a Type 2 Diabetes Susceptibility Gene.
- Authors
Sandhu, Manjinder S.; Weedon, Michael N.; Fawcett, Katherine A.; Wasson, Jon; Debenham, Sally L.; Daly, Allan; Lango, Hana; Frayling, Timothy M.; Neumann, Roz; Blech, Ilana; Pharoah, Paul D.; Palmer, Colin N.; Kimber, Charlotte; Tavendale, Roger; Morris, Andrew D.; Mccarthy, Mark I.; Walker, Mark; Hitman, Graham A.; Glaser, Benjamin; Permutt, M. A.
- Abstract
Deterioration in pancreatic β-cell function is central to the pathophysiology of Type 2 diabetes (T2D). Indeed, genes with important roles in β-cells have been shown to influence susceptibility to this disease. We performed a candidate gene association study examining 1,367 SNPs in 84 β-cell genes in three UK case-control studies. In a log-additive model, 18 SNPs were associated with T2D risk with P<0.01. Further typing in Ashkenazim revealed two SNPs that remained associated with T2D risk (P<0.05) in this population. Both SNPs mapped within the WFS1 gene, and the associations replicated in three further UK case control studies. Pooled analysis of all studies, comprising 9,533 cases and 11,389 controls, showed strong statistical evidence for the association of WFSI SNPs with T2D risk (P≦3.4x10[sup -7]). WFS1 mutations cause Wolfram Syndrome, a rare autosomal recessive syndrome partly characterised by severe juvenile type 2 diabetes. Our data indicate that the WFS1 gene also contributes to risk of common type 2 diabetes (PAT = 9%).
- Subjects
GENES; TYPE 2 diabetes; CELL physiology; PANCREATIC beta cells; GENETIC mutation
- Publication
Diabetes, 2007, Vol 56, pA20
- ISSN
0012-1797
- Publication type
Article