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

Background Progress in identifying genetic factors protective against alcoh ol dependence (AlcD) 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 Aus tralian twin panel. and from a subsample who underwent alcohol challenge, w ere 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 AlcD (risk-inc reasing) were significant and comparable in magnitude. Religious affiliatio n (Anglican versus other) was associated with the ADH2 genotype, but did no t explain the associations with AlcD symptoms. No protective effect of the ADH2*1/*2 genotype was observed in women. Conclusions The early onset and strong familial aggregation of AlcD, and op portunity for within-family tests of genetic association to avoid confoundi ng effects, make epidemiological family studies of adolescents and young ad ults and their families a priority. Declaration of interest This research was supported by grants from the US N ational Institutes of Health, the US Alcohol Beverage Medical Research Foun dation and the Australian National Health and Medical Research Council.