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Kenneth S. Kendler, MD; Carol A. Prescott, PhD

Arch Gen Psychiatry. 1999;56:39-44.

Background  Women report higher rates of major depression (MD) than men. Although genetic factors play an important etiologic role in MD, we are uncertain whether genetic factors are of equal importance in men and women, and whether the same genetic factors predispose men and women to MD.

Methods  We obtained, by telephone interview, a lifetime history of MD, defined by the DSM-III-R, from 3790 complete male-male, female-female, and male-female twin pairs, identified through a population-based registry. Results were analyzed using probandwise concordance, odds ratios, and biometrical twin modeling.

Results  The odds ratios (plus tetrachoric correlations) for lifetime MD were as follows: (1) male-male monozygotic, 3.29 (+0.37); (2) male-male dizygotic, 1.86 (+0.20); (3) female-female monozygotic, 3.02 (+0.39); (4) female-female dizygotic, 1.59 (+0.18); and (5) male-female dizygotic, 1.39 (+0.11). In the best-fitting twin model, the heritability of liability to MD was the same in men and women and equal to 39%, while the remaining 61% of the variance in liability was due to individual-specific environment. We rejected, with only modest confidence, the hypothesis that the genetic risk factors for MD were the same in men and women. The best-fitting model estimated the genetic correlation in the liability to MD in the 2 sexes to be +0.57. While we found no evidence to suggest a violation of the equal environment assumption, MD was less common in women from opposite-sex vs same-sex twin pairs.

Conclusions  Major depression is equally heritable in men and women, and most genetic risk factors influence liability to MD similarly in the 2 sexes. However, genes may exist that act differently on the risk for MD in men vs women.

From the Departments of Psychiatry (Drs Kendler and Prescott) and Human Genetics (Dr Kendler), Medical College of Virgina, Virginia Commonwealth University College of Medicine, Richmond; and the Virginia Institute for Psychiatric and Behavioral Genetics, Richmond (Drs Kendler and Prescott).

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