A POSSIBLE VULNERABILITY LOCUS FOR BIPOLAR AFFECTIVE-DISORDER ON CHROMOSOME 21Q22.3

In a preliminary genome scan of 47 bipolar disorder families, we detec ted in one family a lod score of 3.41 at the PFKL locus on chromosome 21q22.3. The lod score is robust to marker allele frequencies, phenoco py rates and age-dependent penetrance, and remains strongly positive w ith changes in affection status. Fourteen other markers in 21q22.3 wer e tested on this family, with largely positive lod scores. Five of the other 46 families also show positive, but modest lod scores with PFKL . When all 47 families are analysed together, there is little support for linkage to PFKL under homogeneity or heterogeneity using lod score analysis, but the model-free affected-pedigree-member method yields s tatistically significant results (p<0.0003). Our results are consisten t with the presence of a gene in 21q22.3 predisposing at least one fam ily to bipolar disorder.