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A genome screen of a large bipolar affective disorder pedigree supports evidence for a susceptibility locus on chromosome 13q

Molecular Psychiatry volume 6, pages 396–403 (2001)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. In this present study, we undertook a 10 cM genome screen using 400 microsatellite markers in a large multigenerational bipolar pedigree consisting of 40 individuals, including six affecteds. We found strongest evidence for linkage to chromosome 13q14. A maximum NPL score of 4.09 (P = 0.008) was obtained between markers D13S1272 and D13S153 using GENEHUNTER. A maximum two-point LOD score of 2.91 (θ = 0.0) was found for marker D13S153 and a maximum three-point LOD score of 3.0 was obtained between markers D13S291 and D13S153 under a recessive model with 90% maximum age-specific penetrance and including bipolar I and unipolar individuals as affected. Several other markers in the region, D13S175, D13S218, D13S263, and D13S156 had two-point LOD scores greater than 1.5. These results meet the criteria for evidence of suggestive linkage. Haplotype analysis enabled us to narrow the likely disease region to a 6 cM region between markers D13S1272 and D13S1319, which contains the serotonin 2A receptor candidate gene. Two single nucleotide polymorphisms were identified in this gene but we did not detect any significant differences in allele frequency in a case-control sample. The region on chromosome 13q14–32 has previously been implicated in other bipolar and schizophrenia cohorts. Our results provide further support for the existence of a susceptibility locus on chromosome 13q14.

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Acknowledgements

We thank Jim McBride for development of a query database to aid in analysis of the 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 99050), 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, 2010, 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, 2052, Australia

    R F Badenhop & P B Mitchell

  3. Australian Genome Research Facility, Melbourne, 3050, Australia

    K R Ewen

  4. School of Biological Sciences, Macquarie University, Sydney, 2109, 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 a large bipolar affective disorder pedigree supports evidence for a susceptibility locus on chromosome 13q. Mol Psychiatry 6, 396–403 (2001). https://doi.org/10.1038/sj.mp.4000887

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