In this multi‐cohort study, it was shown that CADM2 is associated with multiple substance use and abuse traits, sex‐related risky behavior, and different indices of self‐control. Meta‐analyses showed significant associations between CADM2 and lifetime experience with tobacco and cannabis use, average alcohol and cigarette consumption, regular/problematic alcohol and tobacco use, number of sexual partners, age at first sexual intercourse, and disinhibition. Furthermore, in the per‐sample analyses there were significant associations with sensation seeking, behavioral or substance addiction, and risk‐taking proneness. The variance explained by a single CADM2 SNP ranged from 0.01% (for average alcohol consumption, cigarettes per day, nicotine dependence, and the number of sexual partners) to 0.26% (sensation seeking). Independent top SNPs together explained between 0.07% (regular alcohol use) and 3.02% (regular cannabis use) of the variance. Finally, the self‐control trait “risk‐taking proneness” was found to be a significant partial mediator of the associations between CADM2 and latent factors for lifetime smoking and regular alcohol use.
