1. ¹Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia
2. ²Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
3. ³Prince of Wales Medical Research Institute, Sydney, NSW, Australia
4. ⁴Department of Biological Sciences, Macquarie University, Sydney, NSW, Australia
5. ⁵School of Psychiatry, University of New South Wales, Sydney, NSW, Australia
6. ⁶School of Psychiatry, University of Tasmania, Hobart, Tasmania, Australia
7. ⁷Black Dog Institute, Prince of Wales Hospital, Sydney, NSW, Australia

Correspondence: Professor PR Schofield, Executive Director and CEO, Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney, NSW 2031, Australia. E-mail: p.schofield@unsw.edu.au

Received 17 October 2006; Revised 10 April 2007; Accepted 7 May 2007; Published online 29 January 2008.

Abstract

Bipolar affective disorder is a heritable, relatively common, severe mood disorder with lifetime prevalence up to 4%. We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Z_max-1 linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P=0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25–26 region.