Susceptibility loci for bipolar disorder: overlap with inherited vulnerability to schizophrenia

Genetic epidemiological studies reveal that relatives of bipolar probands are at increased risk for recurrent unipolar, bipolar, and schizoaffective disorders, whereas relatives of probands with schizophrenia are at increased risk for schizophrenia, schizoaffective, and recurrent unipolar disorders. The overlap in familial risk may reflect shared genetic susceptibility. Recent genetic linkage studies have defined confirmed bipolar susceptibility loci for multiple regions of the human genome, including 4p16, 12q24, 18p11.2, 18q22, 21q21, 22q11–13, and Xq26. Studies of schizophrenia kindreds have yielded robust evidence for susceptibility at 18p11.2 and 22q11–13, both of which are implicated in susceptibility to bipolar disorder. Similarly, confirmed schizophrenia vulnerability loci have been mapped, too, for 6p24, 8p, and 13q32. Strong statistical evidence for a 13q32 bipolar susceptibility locus has been reported. Thus, both family and molecular studies of these disorders suggest shared genetic susceptibility. These two groups of disorders may not be as distinct as current nosology suggests.