Bipolar disorder and variation at a common polymorphism (A1832G) within exon 8 of the Wolfram gene

A number of linkage studies provide evidence consistent with the existence of a bipolar susceptibility gene on chromosome 4p16, The gene for Wolfram s yndrome, a rare recessive neurodegenerative disorder, lies in this region a nd has recently been cloned. Psychiatric disturbances including psychosis, mood disorder, and suicide have been reported at increased frequency in Wol fram patients and in heterozygous carriers of a Wolfram mutation. In the cu rrent investigation we have undertaken a case-control association study usi ng a single nucleotide polymorphism (causing an amino acid change) in exon 8 of the Wolfram gene in a UK Caucasian sample of 312 Diagnostic and Statis tical Manual of Mental Disorders (fourth edition; DSM TV) bipolar I proband s and 301 comparison individuals. We found no evidence that variation at th is polymorphism influences susceptibility to bipolar disorder. It remains p ossible that variation at other sites within or near the Wolfram gene plays important roles in determining susceptibility to affective illness. (C) 20 00 Wiley-Liss, Inc.