A third issue is the role of family history, which can indicate inherited vulnerability. Alcohol dependence is highly heritable (Gelernter & Kranzler, 2009). Recent studies in selected samples suggest that among individuals who experience childhood maltreatment, genetic susceptibility increases the risk of various substance phenotypes or their early antecedents (Kaufman et al. 2007; Agrawal et al. 2009; Brody et al. 2009a, b; Caspi et al. 2010; Enoch, 2011). The family history study design is often used as an initial method of exploring genetic issues, for example, in the general population. If at least some individuals in the population require both family history of alcoholism and childhood maltreatment to develop alcohol dependence, then the relationship between these two risk factors will be synergistic (i.e. the joint effect of maltreatment and family history will be greater than the sum of their individual effects) (Rothman et al. 1980). However, whether such a synergistic mechanism exists in the general population is unknown. While the field awaits data from large general population samples to examine this question using molecular genetic variants, synergy can be initially examined using epidemiological information on parental history.
