Genetic risk factors for major depression in men and women: similar or different heritabilities and same or partly distinct genes?

Background. Although women are at consistently greater risk for major depre ssion (MD) than men, it is unclear whether sex modifies the aetiological im pact of genetic factors on MD. Is the heritability of MD different in men a nd women? Do the same genetic risk factors predispose to MD in the two sexe s? Methods. We obtained a lifetime history of MD by personal interview on two occasions from 6672 individual twins and 2974 complete twin pairs. Three di agnostic criteria of increasing narrowness were employed: DSM-III-R, DSM-II I-R plus impairment and Washington University. To increase power by control ling for unreliability of assessment, we evaluated sex differences on genet ic risk for MD using a structural equation measurement model. Results. Using DSM-III-R criteria, but not the two narrower definitions, he ritability of MD was significantly greater in women than in men. In the thr ee diagnostic systems, the genetic correlation in liability to MD in men an d women was estimated at between + 0.50 and + 0.65. These estimates differe d significantly from unity for the two broader definitions. Conclusion. Using broad but not narrower definitions of illness, genetic fa ctors 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 pr obably not entirely the same. These results raiser the possibility that, in linkage and association studies, the impact of some loci on risk for MD wi ll differ in men and women.