Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations.
OBJECTIVE
Mutations at the gene encoding wolframin (WFS1) cause Wolfram syndrome, a rare neurological condition. Associations between single nucleotide polymorphisms (SNPs) at WFS1 and type 2 diabetes have recently been reported. Thus, our aim was to replicate those associations in a northern Swedish case-control study of type 2 diabetes. We also performed a meta-analysis of published and previously unpublished data from Sweden, Finland and France, to obtain updated summary effect estimates.


METHODS
Four WFS1 SNPs (rs10010131, rs6446482, rs752854 and rs734312 [H611R]) were genotyped in a type 2 diabetes case-control study (n = 1,296/1,412) of Swedish adults. Logistic regression was used to assess the association between each WFS1 SNP and type 2 diabetes, following adjustment for age, sex and BMI. We then performed a meta-analysis of 11 studies of type 2 diabetes, comprising up to 14,139 patients and 16,109 controls, to obtain a summary effect estimate for the WFS1 variants.


RESULTS
In the northern Swedish study, the minor allele at rs752854 was associated with reduced type 2 diabetes risk [odds ratio (OR) 0.85, 95% CI 0.75-0.96, p=0.010]. Borderline statistical associations were observed for the remaining SNPs. The meta-analysis of the four independent replication studies for SNP rs10010131 and correlated variants showed evidence for statistical association (OR 0.87, 95% CI 0.82-0.93, p=4.5 x 10(-5)). In an updated meta-analysis of all 11 studies, strong evidence of statistical association was also observed (OR 0.89, 95% CI 0.86-0.92; p=4.9 x 10(-11)).


CONCLUSIONS
In this study of WFS1 variants and type 2 diabetes risk, we have replicated the previously reported associations between SNPs at this locus and the risk of type 2 diabetes.
Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden. paul.franks@medicin.umu.se
P W
PW
Franks
O
O
Rolandsson
S L
SL
Debenham
K A
KA
Fawcett
F
F
Payne
C
C
Dina
P
P
Froguel
K L
KL
Mohlke
C
C
Willer
T
T
Olsson
N J
NJ
Wareham
G
G
Hallmans
I
I
Barroso
M S
MS
Sandhu
D000328:Adult; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D013548:Sweden
D008565:Membrane Proteins; C114987:wolframin protein; D004247:DNA