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Linkage Studies

Individual genetic linkage studies and meta-analyses have identified some chromosomal regions for which there is evidence of linkage in both schizophrenia and bipolar disorder. These include regions of 13q, 22q, 18,^26,27 and 6q.²⁸ The chromosomal regions implicated are wide and contain many genes, so it is not certain that the apparent overlaps reflect the existence of shared genes between the 2 disorders. We should also remember that it remains possible that any given linkage might be a false positive in at least one of the disorders.

However, the hypothesis that loci exist that influence susceptibility across the schizophrenia-bipolar divide has recently received further support from a genome-wide linkage scan using families selected on the basis of a member with DSM-IV schizoaffective disorder, bipolar type. This study demonstrated genome-wide significant linkage at 1q42 and suggestive linkage at 22q11, with evidence for linkage being contributed equally by “schizophrenia” families (ie, those where other members had predominantly schizophrenia) and “bipolar” families (ie, those where other members had predominantly bipolar disorder).²⁹ It is of interest that 2 genes which have been implicated in schizophrenia, DISC1 and catechol - O - methyltransferase (COMT), map to 1q42 and 22q11, respectively, and this raises the question of whether either or both of these genes predispose to illness across the schizophrenia-bipolar divide. There is evidence to support this for both COMT ³⁰ and DISC1 (see below).

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