A genome screen of 35 bipolar affective disorder pedigrees provides signficant evidence for a susceptibility locus on chromosome 15q25-26
McAuley, EZ and Blair, IP and Fullerton, JM and Scimone, A and Van herten, M and Evans, MR and Kirkby, KC and Donald, JA and Mitchell, PB and Schofield, PR and Liu, Z, A genome screen of 35 bipolar affective disorder pedigrees provides signficant evidence for a susceptibility locus on chromosome 15q25-26, Molecular Psychiatry, 14, (5) pp. 492-500. ISSN 1359-4184 (2009) [Refereed Article]
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 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.