Support for the presence of bipolar disorder susceptibility loci on chromosome 5: heterogeneity in a homogeneous population in Quebec.

A very large pedigree derived from the Saguenay-Lac-St-Jean region of Quebec contains a branch where a distal chromosome 5q haplotype seems to cosegregate with bipolar affective disorder. The authors used a diagnosis model where Bipolar Types I and II and schizoaffective disorder bipolar type were considered as affected, while single or recurrent episode major depression was classified as unknown and all the others diagnoses as unaffected. Model-free two-point LOD score values of 3.41 and 2.21 were observed at D5S432 in the 5p region with sib_ibd and sib_phase from the ASPEX package, but simulation studies did not permit the conclusion of a significant linkage because associated empirical P values were equal to .0026 and .0037. A parametric LOD score value of 2.15 was obtained at locus D5S412 in the distal chromosome 5q area. In order to investigate heterogeneity in the single multigenerational family, the pedigree was divided into five branches. Our simulation study suggested that the five branches of the Saguenay-Lac-St-Jean bipolar pedigree had low power to detect linkage under intrapedigree heterogeneity in this region.