Incorporation of molecular data and redefinition of phenotype: new approaches to genetic epidemiology of bipolar manic depressive illness and schizophrenia

Considerable advances have been made in identifying specific genetic components of bipolar manic depressive illness (BP) and schizophrenia (SZ), despite their complex inheritance. Meta-analysis of all published whole-genome linkage scans reveals overall support for illness genes in several chromosomal regions. In two of these regions, on the lonq arm of chromosome 13 and on the long arm of chromosome 22, the combined studies of BP and SZ are consistent with a common susceptibility locus for the two disorders. This lends some plausibility to the hypothesis of some shared genetic predispositions for BP and SZ. Other linkages are supported by multiple studies of specific chromosomal regions, most notably two regions on chromosome 6 in SZ. The velocardiofacial syndrome is associated with deletions very close to the linkage region on chromosome 22, and with psychiatric manifestations of both BP and SZ. Endophenotypes of SZ, previously demonstrated to be heritable, have been found to have chromosomal linkage in at least one study. These include eye-tracking abnormalities linked to the short arm of chromosome 6, and abnormality of the P50 cortical evoked potential linked to chromosome 15. Variants in specific genes have been associated with susceptibility to illness, and other genes have been associated with susceptibility to side effects of pharmacological treatment. These genetic findings may eventually be part of an integrated genetic, environmental, and interactive-factor epidemiology of the major mental illnesses.