We propose to apply GWAS techniques on a single gene, whose candidate‐gene status is anchored in a body of (hypothesis‐free) GWASs. In this first phenome‐wide association study (PHeWAS) 32 for CADM2 and risky behavior, the multiple testing burden is much lower than in GWASs, which should increase power. This study aims to establish if power increases substantially enough to detect associations in smaller samples, thereby also providing insight into gene‐level effect sizes. By looking at several risky behavior phenotypes concurrently, we furthermore investigate the link between genetic variation in CADM2 and substance‐ and sex‐related risk behaviors more comprehensively than single phenotype studies. Doing so, we aim to examine if the involvement of CADM2 in various risky behaviors and self‐control related constructs (i.e., pleiotropy, when a single gene influences the expression of multiple phenotypic traits) can explain the potential genetic overlap between various aspects of reduced self‐control and multiple risky behaviors. By combining data from four different cohorts and analyzing a range of risky behaviors and indices of self‐control, we aim to increase reliability and robustness of findings. 29 Finally, we explore if reduced self‐control might mediate the relationship between CADM2 and various risky behaviors.
