Manhattan (Supplemental figures S11 to S15) and Q-Q plots (Supplemental figures S16 to S20) for the tests of the interaction of the SNP by generation interaction effect are included with the supplementary material. The interaction effect was significant at p < 10-5 for 28 SNPS: 1 for Alcohol Consumption, 11 for Alcohol Dependence, 8 for Illicit Drugs, 3 for Nicotine, and 5 for Behavioral Disinhibition (Supplemental Table 4). The lowest interaction p value of 4 × 10-7 was observed for rs11681792 with the Behavioral Disinhibition phenotype. For none of the 28 SNPs did we observe a second interaction effect at p < 10-5 across the 5 phenotypes, but for 4 of the SNPs we did observe two interaction effects at p < 10-3 in addition to the initial test. These 4 SNPs are listed in Table 3. All 4 SNPs showed a similar pattern of interaction that was consistent across the 5 phenotypes; namely that the SNP effect differed in direction between the parent and offspring generation. This is not unexpected, as the test statistic will be maximized when the
