a clear evidence for additive interaction with AP being 0.67 (95% CI, 0.62–0.72), indicating 67% increased risk is due to synergy. Relative to the reference group, those with high Neuroticism (OR = 1.3, p = .85) or an at-risk SNP (PENK rs2609997; OR = 1.8, p = .26) did not have notable increased risk, but those with high Neuroticism and the at-risk SNP had an over 9-fold increased clinical diagnosis of cannabis dependence (OR = 9.2, p = .0007). A similar additive interaction was detected for the PENK rs2576573 [AP = 0.72, (95% CI, 0.58–0.86)]. Relative to the reference group, those with both at-risk SNP (PENK rs2576773) and high Neuroticism had an over 8-fold increased clinical diagnosis of cannabis dependence (OR = 8.35, p = .001), compared to those with only Neuroticism (OR = 0.93, p = .99) or the at-risk SNP (OR = 2.41, p = .27). It was not possible to study the DRD2 rs6277 SNP due to the high overlap between high Neuroticism and subjects with the G allele.
