Linkage of a bipolar disorder susceptibility locus to human chromosome 13q32 in a new pedigree series.

Bipolar (BP) disorder or manic depressive illness is a major psychiatric disorder for which numerous family, twin and adoption studies support a substantial genetic contribution. Recently, we reported the results of a genome-wide search for BP disorder susceptibility loci in 20 pedigrees. Suggestive evidence for linkage was found in this study at three markers on 13q, representing possibly two peaks separated by 18 cM. We have now collected a second set of 32 pedigrees segregating BP disorder and have tested for evidence of linkage to markers on human chromosome 13q. In this sample, we have replicated the linkage result in 13q32 at D13S154 (lod=2.29), the more proximal of the two original peaks. When all 52 pedigrees were combined, the multipoint maximum lod score peaked approximately 7 cM proximal to D13S154 (lod=3.40), with a second peak occurring between D13S225 and D13S796 (lod=2.58). There have been several other reports of significant linkage to both BP disorder and schizophrenia in this region of chromosome 13. These pedigrees provide additional evidence for at least one locus for BP disorder in 13q32, and are consistent with other reports of a possible genetic overlap between these disorders.