Twin and adoption studies indicate that genetic factors are likely to substantially influence alcohol-related behavioral phenotypes, including alcohol dependence (McGue, 1999), and quantitative measures of alcohol use (Heath and Martin, 1994). However, few individual common genetic variants have been consistently shown to have replicable effect upon alcohol use and dependence. One reason genetic association studies might fail to account for a substantial proportion of the genetic variance suggested by biometrical analyses is if the variants underlying variation in alcohol-related phenotypes are of such small individual effect that markers tagging them do not meet thresholds for significance. Genes that belong to biological systems or pathways relevant to the effects of alcohol and have been repeatedly implicated in previous studies might be more likely to yield evidence for genetic effects reflecting the mechanisms underlying alcohol use related behaviors.
