Genome wide scan using homozygosity mapping and linkage analyses of a single pedigree with affective disorder suggests oligogenic inheritance.

The present study reports results from a genome scan on a family with bipolar affective disorder in which the parents are first cousins and four of the offsprings and one grandchild have affective disorder. The study searched for risk loci for affective disorder by searching for homozygous segments or more complex inherited loci using parametric and non-parametric multipoint linkage analysis. In addition dominant, multipoint, affecteds-only linkage analyses were performed as a supplement to previous analyses. On chromosomes 2q31.3, 10, 12q24, and 21q22.3 evidence for a risk locus was obtained by parametric and/or non-parametric linkage analyses and by haplotype sharing. As other studies have found significant or suggestive linkage to bipolar disorder in these chromosome regions this suggests that an oligogenic mode of inheritance is possible in this family involving at least some of the loci. Finally, the work discusses whether homozygosity mapping using parametric and non-parametric linkage analyses may be of value for complex diseases including rare subphenotypes of such disorders.