Future studies should, first, strive to examine joint and interactive effects of the genetic markers because interaction effects could account for some of the inconsistent findings. Second, future investigations should also ideally consider longitudinal or prospective studies. Such studies can improve the understanding of the genetic mechanism and how the effects will change over the course of lifetime substance use. Third, most inherited AD involves the interaction of multiple genes that have minor effects and sociocultural factors. For example, increased cultural acceptance of alcohol consumption has been shown to reduce the protective effect of the ALDH2 350Val allele(Higuchi et al. 1994); thus, gene-environment interactions should also be considered in the future studies. Fourth, to identify genes of minor effect, alcohol dependent subjects with either heterozygous Ile350Val or homozygous Val350Val, could be selected based on their reduced heterogeneity. Fifth, quantitative tests may be of value. In addition, future studies should use older control samples that can be more accurately categorized, as younger individuals may not have fully transited the age of risk for alcohol dependence.
