ABSTRACT
Familial liability to bipolar disorder has been recognized since the clinical syndrome was introduced a century ago, and twin studies have further demonstrated that such familiality is related to genetic transmission of the illness.2 The heritability of operationally defined bipolar disorder is estimated to be over 80%, similar to that of other psychotic disorders such as schizophrenia,2,3 with the remaining variance attributable to non-shared environmental risk factors. Clearly, susceptibility genes must exist for this illness, but progress in identifying such genes has been exceedingly slow, owing to the complexity of genetic transmission. There are unlikely to be any genes of major effect for bipolar disorder, expect perhaps in some rare pedigrees, and instead inheritance is probably due to many genes of small effect. Furthermore, the molecular genetics research of bipolar disorder, like many other psychiatric disorders, is hindered by the inaccuracy of phenotypic definition; we lack laboratory diagnostic tests, even at postmortem, and the use of the clinical syndrome alone as the phenotype is problematic because of the effects of genetic heterogeneity and reduced penetrance.
