The International Journal of Neuropsychopharmacology



Polymorphisms in wolframin (WFS1) gene are possibly related to increased risk for mood disorders


Kati Koido a1, Sulev Kõks a1a4c1, Tiit Nikopensius a2, Eduard Maron a3, Signe Altmäe a2, Evelin Heinaste a2, Kristel Vabrit a2, Veronika Tammekivi a2, Pille Hallast a2, Ants Kurg a2, Jakov Shlik a3, Veiko Vasar a3, Andres Metspalu a2a5 and Eero Vasar a1a4
a1 Department of Physiology, University of Tartu, Tartu, Estonia
a2 Institute of Molecular and Cell Biology and Estonian Biocentre, University of Tartu, Tartu, Estonia
a3 Department of Psychiatry, University of Tartu, Estonia
a4 Visgenyx Ltd, Tartu, Estonia
a5 Asper Biotech Ltd, Tartu, Estonia

Article author query
koido k   [PubMed][Google Scholar] 
koks s   [PubMed][Google Scholar] 
nikopensius t   [PubMed][Google Scholar] 
maron e   [PubMed][Google Scholar] 
altmae s   [PubMed][Google Scholar] 
heinaste e   [PubMed][Google Scholar] 
vabrit k   [PubMed][Google Scholar] 
tammekivi v   [PubMed][Google Scholar] 
hallast p   [PubMed][Google Scholar] 
kurg a   [PubMed][Google Scholar] 
shlik j   [PubMed][Google Scholar] 
vasar v   [PubMed][Google Scholar] 
metspalu a   [PubMed][Google Scholar] 
vasar e   [PubMed][Google Scholar] 

Abstract

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.

(Received March 17 2004)
(Reviewed June 20 2004)
(Revised July 11 2004)
(Accepted July 18 2004)


Key Words: Association; bipolar disorder; genetics; haplotype analysis; major depressive disorder; single-nucleotide polymorphism (SNP); WFS1; wolframin.

Correspondence:
c1 Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. Tel.: +372 7 374 335 Fax: +372 7 374 332 E-mail: Sulev.Koks@ut.ee