The causal inference literature indicates that synergy is most closely represented by interaction effects on the additive risk scale, which can be assessed with attributable proportions due to interaction (APs) (Rothman et al. 1980; Darroch, 1997). Therefore, to assess for synergy between parental history of alcohol dependence and each childhood maltreatment (Aim 4), APs and 95% CIs were obtained for each maltreatment according to the method of Andersson et al. (2005) which has been used extensively in previous analyses of additive interactions with binary outcomes (e.g. Wicks et al. 2010; Zhang et al. 2010). APs were calculated using the formula (OR11 − OR10 − OR01+1)/ OR11 (Rothman et al. 1980; Kalilani & Atashili, 2006) which tests whether the joint effect of the maltreatment and parental history (OR11) differs from the sum of the effect of the maltreatment in the absence of parental history (OR10) and the effect of parental history in the absence of the maltreatment (OR01). An AP of 0 indicates no effect modification (i.e. that OR11=OR10+OR01), while an AP greater than 0 indicates synergy (i.e. that OR11>OR10+OR01). Significant APs are those whose 95% CIs do not include 0. Analyses adjusted for demographics and other adverse childhood experiences.
