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

E. Z. McAuley, I. P. Blair, Z. Liu, J. M. Fullerton, A. Scimone, M. Van Herten, M. R. Evans, K. C. Kirkby, J. A. Donald, P. B. Mitchell, P. R. Schofield

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23 Citations (Scopus)

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(max1) linkage confidence interval of 17cM, or 6.2Mb, 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 (P0.0008) obtained at 107.16cM (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.

Original languageEnglish
Pages (from-to)492-500
Number of pages9
JournalMolecular Psychiatry
Volume14
Issue number5
DOIs
Publication statusPublished - May 2009

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