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Shared Genetic Risk of Major Depression, Alcohol Dependence, and Marijuana Dependence
Contribution of Antisocial Personality Disorder in Men
Qiang Fu, MD,PhD;
Andrew C. Heath, DPhil;
Kathleen K. Bucholz, PhD;
Elliot Nelson, MD;
Jack Goldberg, PhD;
Michael J. Lyons, PhD;
William R. True, PhD,MPH;
Theodore Jacob, PhD;
Ming T. Tsuang, MD,PhD,DSc;
Seth A. Eisen, MD,MSc
Arch Gen Psychiatry. 2002;59:1125-1132.
Background Little is known about genetic factors that underlie the interrelationships among antisocial personality disorder (ASPD), major depression (MD), alcohol dependence (AD), and marijuana dependence (MJD). We examined the contribution of genetic effects associated with ASPD to the comorbidity of MD and substance use disorders.
Methods The Vietnam Era Twin Registry is a general population registry of male veteran twins constructed from computerized Department of Defense files and other sources. A telephone diagnostic interview was administered to eligible twins from the Registry in 1992. Of 5150 twin pairs who served on active military duty during the Vietnam era, 3360 pairs (1868 monozygotic and 1492 dizygotic) in which both members completed the pertinent diagnostic interview sections were included. The main outcome measures were lifetime DSM-III-R ASPD, MD, AD, and MJD.
Results Structural equation modeling was performed to estimate additive genetic, shared environmental, and nonshared environmental effects common and specific to each disorder. The heritability estimates for lifetime ASPD, MD, AD, and MJD were 69%, 40%, 56%, and 50%, respectively. Genetic effects on ASPD accounted for 38%, 50%, and 58% of the total genetic variance in risk for MD, AD, and MJD, respectively. After controlling for genetic effects on ASPD, the partial genetic correlations of MD with AD and with MJD were no longer statistically significant. Genetic effects specific to MD and AD and familial effects specific to MJD remained statistically significant. Nonshared environmental contributions to the comorbidity in these disorders were small.
Conclusions In this sample, the shared genetic risk between MD and both AD and MJD was largely explained by genetic effects on ASPD, which in turn was associated with increased risk of each of the other disorders.
From the Missouri Alcoholism Research Center at Washington University, Departments of Psychiatry (Drs Fu, Heath, Bucholz, and Nelson) and Internal Medicine (Dr Eisen), Washington University School of Medicine, St Louis, Mo; the Department of Veterans Affairs, Vietnam Era Twin Registry/Seattle Epidemiologic Research and Information Center, Seattle, Wash (Dr Goldberg); the Department of Epidemiology, University of Washington School of Public Health, Seattle (Dr Goldberg); the Department of Psychology, Boston University, Boston, Mass (Dr Lyons); the Institute of Psychiatric Epidemiology and Genetics, Harvard Medical School, Boston (Drs Lyons and Tsuang); Saint Louis University School of Public Health, St Louis (Drs Fu and True); Research and Medical Service, St Louis VA Medical Center, St Louis (Drs True and Eisen); VA Palo Alto Health Care System, Palo Alto, Calif (Dr Jacob); Harvard Medical School Department of Psychiatry at Massachusetts Mental Health Center, Boston (Dr Tsuang); and the Department of Epidemiology, Harvard School of Public Health, Boston (Dr Tsuang).
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