In the alcohol field, past experiences with case control studies of genetic association have been disappointing (e.g., Blum et al. 1990; Gelernter et al. 1993). It is possible, however, that with increased sample sizes and stringent statistical criteria for accepting a genetic association, such inconsistencies will disappear (e.g., Morton and Collins 1998). The validity of this approach has been demonstrated in the field of cardiovascular genetics, where studies contrasting as many as 5,000 cases and 5,000 control subjects have been completed (e.g., Cardon and Bell 2001). Such a sample size is adequate to analyze the effects of multiple genetic risk factors that individually have only modest effects on risk, as well as their interactions. Even such large case control studies have some limitations for establishing the effects of various environmental risk factors and their interactions with genetic factors. These limitations result from the retrospective design, which makes it difficult to reliably establish the participants’ past history of risk-factor exposure. To address this issue, large prospective cohort studies of adults, involving up to 500,000 participants, are being planned (Meade et al.
