Common variants in WFS1 confer risk of type 2 diabetes.
We studied genes involved in pancreatic beta cell function and survival, identifying associations between SNPs in WFS1 and diabetes risk in UK populations that we replicated in an Ashkenazi population and in additional UK studies. In a pooled analysis comprising 9,533 cases and 11,389 controls, SNPs in WFS1 were strongly associated with diabetes risk. Rare mutations in WFS1 cause Wolfram syndrome; using a gene-centric approach, we show that variation in WFS1 also predisposes to common type 2 diabetes.
Sandhu
Manjinder S
MS
UK Medical Research Council (MRC) Epidemiology Unit, Strangeways Research Laboratory, Cambridge CB1 8RN, UK. manj.sandhu@srl.cam.ac.uk
Weedon
Michael N
MN
Fawcett
Katherine A
KA
Wasson
Jon
J
Debenham
Sally L
SL
Daly
Allan
A
Lango
Hana
H
Frayling
Timothy M
TM
Neumann
Rosalind J
RJ
Sherva
Richard
R
Blech
Ilana
I
Pharoah
Paul D
PD
Palmer
Colin N A
CN
Kimber
Charlotte
C
Tavendale
Roger
R
Morris
Andrew D
AD
McCarthy
Mark I
MI
Walker
Mark
M
Hitman
Graham
G
Glaser
Benjamin
B
Permutt
M Alan
MA
Hattersley
Andrew T
AT
Wareham
Nicholas J
NJ
Barroso
Inês
I
D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D008565:Membrane Proteins; C114987:wolframin protein