Supportive evidence for a bipolar susceptibility gene on chromosome 4q35

Recently evidence for a gene of susceptibility for bipolar disorder was reported on chromosome 4q35 [Adams et al., 1998]. We present supportive data for a gene of bipolar susceptibility on chromosome 4q35. We have ascertained 51 pedigrees through a treated BPI proband. All subjects were evaluated using the SADS-L and diagnosed using the Research Diagnostic Criteria (RDC). As part of a genome-wide screen, we have genotyped markers at 5-10 cM intervals. We report here on the findings for chromosome 4. As part of our original design, the pedigrees were divided into the initial group of 28 pedigrees [Stine et al., 1995] and a second set of 23 pedigrees. The analyses were done on each family set and then on all the pedigrees together. Analyses were done using Genehunter. We found no evidence supporting a bipolar susceptibility locus in the region of 4p described by Blackwood et al. [1996]. The findings were strongest at the marker D4S3032. On the initial set of 28 pedigrees, the NPL = 1.9, P = 0.04; HLOD = 0.6. On the second set of 23 pedigrees, the NPL was 2.0, P = 0.03; HLOD = 0.9. The combined data set produced an NPL = 2.6, P = 0.007, and HLOD = 1.5. Although supportive, these data do not reach the most stringent criteria for the presence of a gene for susceptibility.