A single major locus model of inheritance that incorporates polarity (bipolar-unipolar distinction) and sex effect was applied to family study data on bipolar and unipolar affective disorders. In the model tested, clinical polarity and sex-related thresholds determined a differential liability to major affective illness, whereby unipolar females and bipolar males represented two extremes on a genetic-environmental continuum. Bipolar males were more deviant, and unipolar females were less deviant genetically than bipolar females and unipolar males. The major locus hypothesis did not provide an acceptable fit to the data. The implications of these findings for genetic and biological research in affective disorders are discussed.

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