Wolfram syndrome gene (WFS1) has been suggested to have a role in the susceptibility for mood disorders. A 26-fold increased risk for psychiatric disorders in WFS1 mutation carriers has been suggested. In this study we tested the hypothesis that the WFS1 gene is related to the risk for mood disorders. We analysed 28 single-nucleotide polymorphisms (SNPs) of the WFS1 gene in 224 unrelated patients with major depressive disorder and bipolar disorder and in 160 healthy control subjects. Patients were further stratified according to their comorbidity with anxiety disorders. We applied arrayed primer extension (APEX)-based genotyping technology followed by association and haplotype analysis. Five SNPs in the WFS1 gene were associated with major depressive disorder, and three SNPs with bipolar disorder. Haplotype analysis revealed a common GTA haplotype, formed by SNPs 684C/G, 1185C/T and 1832G/A, conferring risk for affective disorders. Specifically, for major depression the GTA haplotype has an OR of 1.59 (p=0.01) and for bipolar disorder an OR of 1.89 (p=0.03). These results support the hypothesis that the WFS1 gene is involved in the genetic predisposition for mood disorders.
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