A linkage disequilibrium study of bipolar disorder and microsatellite markers on 22q13

Bipolar disorder is a major psychiatric disorder characterized by extreme mood states that alternate between mania and depression. Family, twin, and adoption studies indicate a genetic component to the disease, but the etiology is suspected to be complex, with multiple genes contributing to an increased susceptibility to the disorder. We have previously reported a genome scan in which a genome-wide maximum LOD score indicated evidence of linkage at the marker D22S278 at 22q13. This area is of particular interest since it is also implicated in schizophrenia, and thus may harbor a susceptibility gene common to both disorders. In our further efforts to fine map this region, we examined 10 microsatellite markers spanning an interval of 2.3 MB in a set of 142 parent-proband triads. Linkage disequilibrium to illness was tested using the Transmission Disequilibrium Test. Haplotypes were determined and marker-to-marker linkage disequilibrium across the region was examined. D22S281 and D22S685 yielded suggestive evidence of linkage disequilibrium to bipolar disorder (empirical values of 0.023 and 0.036, respectively), but a marker-to-marker analysis indicates that a higher density screen is needed to adequately analyze this region.