Background. Although women are at consistently greater risk for major depression (MD) than men, it is unclear whether sex modifies the aetiological impact of genetic factors on MD. Is the heritability of MD different in men and women? Do the same genetic risk factors predispose to MD in the two sexes?

Methods. We obtained a lifetime history of MD by personal interview on two occasions from 6672 individual twins and 2974 complete twin pairs. Three diagnostic criteria of increasing narrowness were employed: DSM-III-R, DSM-III-R plus impairment and Washington University. To increase power by controlling for unreliability of assessment, we evaluated sex differences on genetic risk for MD using a structural equation measurement model.

Results. Using DSM-III-R criteria, but not the two narrower definitions, heritability of MD was significantly greater in women than in men. In the three diagnostic systems, the genetic correlation in liability to MD in men and women was estimated at between +0·50 and +0·65. These estimates differed significantly from unity for the two broader definitions.

Conclusion. Using broad but not narrower definitions of illness, genetic factors play a greater role in the aetiology of MD in women than in men. The genes that influence risk for MD in the two sexes are correlated but are probably not entirely the same. These results raise the possibility that, in linkage and association studies, the impact of some loci on risk for MD will differ in men and women.