Background:
Bipolar affective disorder (BP) is a relatively common, severe mood disorder characterized by periods of mania and depression, with estimates of lifetime prevalence up to 4%.
Method:
We conducted a 10-cM genome scan on 35 multigenerational pedigrees with 288 genotyped individuals (130 affected according to a broad disease definition). Subsequent fine mapping was conducted on the region with significant linkage results and was assessed using parametric, nonparametric and multipoint linkage analysis methods, as well as haplotype analysis based on pedigree-specific, identical-by-descent allele sharing.
Results:
The genome scan identified significant linkage on chromosome 15q25-26 and suggestive evidence on chromosomes 4q, 6q and 13q. Analysis of the 15q25-26 region, including additionally typed chromosome 15q markers, gave significant results with a maximum two-point LOD score of 3.38 and a multipoint LOD score of 4.58 for marker D15S130. A maximum NPL score of 3.38 (P = 0.0008) was obtained at 107.16 cM near D15S130. The 95% confidence interval estimation suggested a support interval spanning 17 cM between the markers D15S979 and D15S816. Haplotype analysis supported the 95% confidence interval estimates.
Conclusions:
The significant and supporting results from a number of analysis methods performed on chromosome 15q25-26 provide evidence for a BP susceptibility locus in this region. It is further supported by linkage findings from studies on recurrent early-onset major depressive disorder, BP with psychotic features, and a study of schizophrenic and BP subjects, suggesting that the locus might contain a gene conferring susceptibility to both mood and psychotic disorders.
