using mixed sex samples, especially when this affects sex matching between cases or controls. Fifth, the genetic effects of ADH1C 350Ile may change over the course of lifetime alcohol use. For example, it may be a protective factor at one stage, but become a neutral or even a risk factor at another stage(Lenroot and Giedd 2008). Sixth, potential cultural differences in patterns of alcohol consumption (and potentially in reporting or diagnosing) consititute one easily idendifiable set of environmental influences on this trait, and can also contribute to discrepancies by interacting with the effect of variation at the gene.