Towards a molecular epidemiology of alcohol dependence: Analysing the interplay of genetic and environmental risk factors

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Abstract
Background: Progress in identifying genetic factors protective against alcohol dependence (AIcD) requires a paradigm shift in psychiatric epidemiology.Aims: To integrate analysis of research into the genetics of alcoholism.Method: Data from prospective questionnaire and interview surveys of the Australian twin panel, and from a subsample who underwent alcohol challenge, were analysed.Results: In men, effects of alcohol dehydrogenase ADH2∗1/∗2 genotype or high alcohol sensitivity (risk-decreasing), and of history of childhood conduct disorder, or having monozygotic co-twin or twin sister with AIcD (risk-increasing) were significant and comparable in magnitude. Religious affiliation (Anglican versus other) was associated with the ADH2 genotype, but did not explain the associations with AIcD symptoms. No protective effect of the ADH2∗1/∗2 genotype was observed in women.Conclusions: The early onset and strong familial aggregation of AIcD, and opportunity for within-family tests of genetic association to avoid confounding effects, make epidemiological family studies of adolescents and young adults and their families a priority.