Fig. 3: Potential power for 2-step approach.

We plotted for each environmental exposure, current drinking (a), drinking habits (b), current smoking (c) and ever smoking (d), the proportion of independent SNPs displaying an interaction p value (P_int) below 0.05 in CHARGE across bins of variants selected from an independent marginal effect GWAS. Those bins were defined as sets of independent variants with p value for marginal genetic effect (P_marg) lower than a given threshold (x axis). Each of the five phenotypes are represented by a plain color line. All analyses used stage 1 1df interaction results from European ancestry individuals. Under the null hypothesis of no correlation, the proportion follows a binomial distribution with parameter 0.05 (the black dashed line), independent of the threshold for P_marg. Gray areas indicate the Wilson score confidence interval for an alpha threshold of 0.05 (dark gray) and 1 × 10⁻⁴ (light gray).