Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk

Background. Substantial evidence exists for an important genetic contributi on to alcohol dependence risk in women and men. It has been suggested that genetically determined differences in alcohol sensitivity may represent one pathway by which an increase in alcohol dependence risk occurs. Methods. Telephone interview follow-up data were obtained on twins from mal e, female and unlike-sex twin pairs who had participated in an alcohol chal lenge study in 1979-81, as well as other pairs from the same Australian twi n panel surveyed by mail in 1980-82. Results. At follow-up, alcohol challenge men did not differ from other male twins from the same age cohort on measures of lifetime psychopathology or drinking habits; but alcohol challenge women were on average heavier drinke rs than other women. A composite alcohol sensitivity measure, combining sub jective intoxication and increase in body-sway after alcohol challenge in 1 979-81, exhibited high heritability (60%). Parental alcoholism history was weakly associated with decreased alcohol sensitivity in women, but not afte r adjustment for baseline drinking history, or in men. High alcohol sensiti vity in men was associated with substantially reduced alcohol dependence ri sk (OR = 0.05, 95% CI 0.01-0.39). Furthermore, significantly decreased (i.e ; low) alcohol sensitivity was observed in non-alcoholic males whose MZ co- twin had a history of alcohol dependence, compared to other non-alcoholics. These associations remained significant in conservative analyses that cont rolled for respondents' alcohol consumption levels and alcohol problems in 1979-81. Conclusions. Men (but not women) at increased genetic risk of alcohol depen dence (assessed by MZ co-twin's history of alcohol dependence) exhibited re duced alcohol sensitivity. Associations with parental alcoholism were incon sistent.