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New Insights Using an Offspring-of-Twins Design

Theodore Jacob, PhD; Brian Waterman, MPH; Andrew Heath, PhD; William True, PhD, MPH; Kathleen K. Bucholz, PhD; Randy Haber, PhD; Jeff Scherrer, MA; Qiang Fu, MD, PhD

Arch Gen Psychiatry. 2003;60:1265-1272.

Context  Although there is now considerable evidence that genetic effects play a critical role in the development of alcohol dependence (AD), theoretical and methodological limitations of this literature require caution in describing the etiology and development of this disorder.

Objective  To disentangle genetic and environmental effects on AD by means of the infrequently used, yet potentially powerful, offspring-of-twins design.

Design  Offspring of twins.

Participants  Male monozygotic and dizygotic twins concordant or discordant for AD and control pairs from the Vietnam Era Twin Registry were assessed, as were the offspring of these twins and the mothers of these offspring.

Interventions  Structured psychiatric interviews.

Main Outcome Measures  Participants' psychiatric, alcohol abuse (AA), and AD histories (DSM-IV).

Results  Offspring of monozygotic and dizygotic twins with a history of AD were significantly more likely to exhibit AA or AD than were offspring of nonalcoholic fathers. Offspring of an alcohol-abusing monozygotic twin whose co-twin was AD were also more likely to exhibit AD than were offspring of nonalcoholic twins. In contrast, offspring of an unaffected (ie, no history of abuse or dependence) monozygotic twin whose co-twin was AD were no more likely to exhibit AA or AD than were offspring of nonalcoholic twins.

Conclusions  These findings support the hypothesis that family environmental effects do make a difference in accounting for offspring outcomes, in particular, that a low-risk environment (ie, the absence of parental alcoholism) can moderate the impact of high genetic risk regarding offspring for the development of alcohol-use disorders.

From the Palo Alto Veterans Affairs Health Care System, Menlo Park, Calif (Drs Jacob and Haber); the Saint Louis Veterans Affairs Medical Center, St Louis, Mo (Mr Waterman); the Department of Psychiatry, Washington University School of Medicine, St Louis (Drs Heath and Bucholz); and the School of Public Health, St Louis University (Drs True and Fu and Mr Scherrer).

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