Genetics of bipolar affective disorder

Bipolar affective disorder is a highly heritable condition, as demonstrated in twin, family, and adoption studies. Morbid risk in first degree relatives is four to six times higher than the population prevalence of about 1%. However, the mode of inheritance is complex, and linkage findings have been difficult to replicate. Despite these limitations, consistent linkage findings have emerged on several chromosomes, notably 18p, 18q, 21q, 12q, 4p, and Xq. Two additional areas, 10p and 13q, have shown linkage in regions that appear to overlap with significant linkage findings in schizophrenia. Separate linkage studies in schizophrenia also have targeted the replicated bipolar linkages on 18p and 22q. New methods are being developed for fine mapping and candidate identification. Recent candidate gene studies include some positive results for the serotonin transporter gene on 17q and the catechol-o-methyltransferase gene on 22q. No other candidate gene studies are yet showing replicated results. A convincing demonstration for a susceptibility gene will probably require a mixture of case- control studies, family-based association methods, and pathophysiologic studies.