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A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26

Molecular Psychiatry volume 14, pages 492–500 (2009)Cite this article

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 Zmax−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.

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Acknowledgements

We thank all patients and family members who participated in this study. We also thank Jim McBride and the staff of the Peter Wills Bioinformatic Centre, Garvan Institute of Medical Research, Sydney, Australia, for their IT assistance. This study was supported by the National Health and Medical Research Council (NHMRC) (Australia) Dora Lush Scholarship (325641) to EZM, Senior Principal Research Fellowship (157209) to PRS, Project Grant (230802) and Program Grant (223708).

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Authors and Affiliations

  1. Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia

    E Z McAuley, I P Blair, J M Fullerton, A Scimone & P R Schofield

  2. Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

    E Z McAuley, I P Blair & P R Schofield

  3. Prince of Wales Medical Research Institute, Sydney, NSW, Australia

    E Z McAuley, J M Fullerton, A Scimone & P R Schofield

  4. Department of Biological Sciences, Macquarie University, Sydney, NSW, Australia

    Z Liu & J A Donald

  5. School of Psychiatry, University of New South Wales, Sydney, NSW, Australia

    M Van Herten, M R Evans & P B Mitchell

  6. School of Psychiatry, University of Tasmania, Hobart, Tasmania, Australia

    M R Evans & K C Kirkby

  7. Black Dog Institute, Prince of Wales Hospital, Sydney, NSW, Australia

    P B Mitchell

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  1. E Z McAuley
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Correspondence to P R Schofield.

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Australian Genome Research Facility http://www.agrf.org.au

Ensembl http://www.ensembl.org/

The Genome Database (GDB) http://www.gdb.org

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McAuley, E., Blair, I., Liu, Z. et al. A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26. Mol Psychiatry 14, 492–500 (2009). https://doi.org/10.1038/sj.mp.4002146

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