This comprehensive multi‐cohort study has shown the feasibility of a PHeWAS for risky behavior to confirm previous findings on associations between CADM2 and manifestations of risky behavior and reduced self‐control from GWASs on individual phenotypes. It was shown that single SNPs in CADM2 could explain 0.01% to 0.26% of the variance and a combination of independent top SNPs together 0.07% to 3.02%. This study provides more insight into the relatively small effect sizes that can be expected from association studies. Furthermore, results revealed that a self‐control trait might partially mediate the associations between CADM2 and substance‐related risky behavior (lifetime smoking and regular alcohol use). Future studies should further explore the biological underpinnings of the observed relationships between CADM2, reduced self‐control, and various risky behaviors.
