A genome screen of a large bipolar affective disorder pedigree supports evidence for a susceptibility locus on chromosome 13q

Bipolar affective disorder is a severe mood disorder that afflicts approxim ately 1% of the population worldwide. Twin and adoption studies have indica ted that genetic factors contribute to the disorder and while many chromoso mal regions have been implicated, no susceptibility genes have been identif ied. In this present study, we undertook a 10 cM genome screen using 400 mi crosatellite markers in a large multigenerational bipolar pedigree consisti ng of 40 individuals, including six affecteds. We found strongest evidence for linkage to chromosome 13q14. A maximum NPL score of 4.09 (P = 0.008) wa s obtained between markers D13S1272 and D13S153 using GENEHUNTER. A maximum two-point LOD score of 2.91 (theta = 0.0) was found for marker D13S153 and a maximum three-point LOD score of 3.0 was obtained between markers D13S29 1 and D13S153 under a recessive model with 90% maximum age-specific penetra nce and including bipolar I and unipolar individuals as affected. Several o ther markers in the region, D13S175, D13S218, D13S263, and D13S156 had two- point LOD scores greater than 1.5. These results meet the criteria for evid ence of suggestive linkage. Haplotype analysis enabled us to narrow the lik ely disease region to a 6 cM region between markers D13S1272 and D13S1319, which contains the serotonin 2A receptor candidate gene. Two single nucleot ide polymorphisms were identified in this gene but we did not detect any si gnificant differences in allele frequency in a case-control sample. The reg ion on chromosome 13q14-32 has previously been implicated in other bipolar and schizophrenia cohorts. Our results provide further support for the exis tence of a susceptibility locus on chromosome 13q14.