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A genome screen of 13 bipolar affective disorder pedigrees provides evidence for susceptibility loci on chromosome 3 as well as chromosomes 9, 13 and 19

Molecular Psychiatry volume 7, pages 594–603 (2002)Cite this article

Abstract

Bipolar affective disorder is a severe mood disorder that afflicts approximately 1% of the population worldwide. Twin and adoption studies have indicated that genetic factors contribute to the disorder and while many chromosomal regions have been implicated, no susceptibility genes have been identified. We undertook a combined analysis of 10 cM genome screen data from a single large bipolar affective disorder pedigree, for which we have previously reported linkage to chromosome 13q14 (Badenhop et al, 2001) and 12 pedigrees independently screened using the same 400 microsatellite markers. This 13-pedigree cohort consisted of 231 individuals, including 69 affected members. Two-point LOD score analysis was carried out under heterogeneity for three diagnostic and four genetic models. Non-parametric multipoint analysis was carried out on regions of interest. Two-point heterogeneity LOD scores (HLODs) greater than 1.5 were obtained for 11 markers across the genome, with HLODs greater than 2.0 obtained for four of these markers. The strongest evidence for linkage was at 3q25–26 with a genome-wide maximum score of 2.49 at D3S1279. Six markers across a 50 cM region at 3q25–26 gave HLODs greater than 1.5, with three of these markers producing scores greater than 2.0. Multipoint analysis indicated a 20 cM peak between markers D3S1569 and D3S1614 with a maximum NPL of 2.8 (P= 0.004). Three other chromosomal regions yielded evidence for linkage: 9q31–q33, 13q14 and 19q12–q13. The regions on chromosomes 3q and 13q have previously been implicated in other bipolar and schizophrenia studies. In addition, several individual pedigrees gave LOD scores greater than 1.5 for previously reported bipolar susceptibility loci on chromosomes 18p11, 18q12, 22q11 and 8p22–23.

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Acknowledgements

We thank Jim McBride for development of a query database to aid in analysis of the linkage data, John Barlow and staff of the Australian Genome Research Facility, Melbourne, Australia and the family members who participated in this study. This study was supported by the National Health and Medical Research Council (Australia) via grants to the Garvan Institute of Medical Research (Block grant 993050), the Mood Disorders Unit, Prince of Wales Hospital (Program Grant 993208) and the Network of Brain Research into Mental Disorders (Unit Grant 983302).

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Authors and Affiliations

  1. Garvan Institute of Medical Research, Sydney, Australia

    R F Badenhop, M J Moses, A Scimone, A Rosso, L J Adams & P R Schofield

  2. School of Psychiatry, University of New South Wales and Mood Disorders Unit, Prince of Wales Hospital, Sydney, Australia

    R F Badenhop & P B Mitchell

  3. Australian Genome Research Facility, Melbourne, Australia

    K R Ewen-White

  4. School of Biological Sciences, Macquarie University, Sydney, Australia

    J A Donald

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  1. R F Badenhop
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Correspondence to P R Schofield.

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Badenhop, R., Moses, M., Scimone, A. et al. A genome screen of 13 bipolar affective disorder pedigrees provides evidence for susceptibility loci on chromosome 3 as well as chromosomes 9, 13 and 19. Mol Psychiatry 7, 594–603 (2002). https://doi.org/10.1038/sj.mp.4001025

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