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Recent genome\u2010wide association studies indicated that variation in the cell adhesion molecule 2 (<jats:italic>CADM2<\/jats:italic>) gene plays a role in risky behaviors and self\u2010control. In this phenome\u2010wide scan for risky behavior, it was tested if underlying common vulnerability could be (partly) explained by pleiotropic effects of this gene and how large the effects were. Single nucleotide polymorphism (SNP)\u2010level and gene\u2010level association tests within four samples (25 and Up, Spit for Science, Netherlands Twin Register, and UK Biobank and meta\u2010analyses over all samples (combined sample of 362,018 participants) were conducted to test associations between<jats:italic>CADM2<\/jats:italic>, substance\u2010 and sex\u2010related risk behaviors, and various measures related to self\u2010control. We found significant associations between the<jats:italic>CADM2<\/jats:italic>gene, various risky behaviors, and different measures of self\u2010control. The largest effect sizes were found for cannabis use, sensation seeking, and disinhibition. Effect sizes ranged from 0.01% to 0.26% for single top SNPs and from 0.07% to 3.02% for independent top SNPs together, with sufficient power observed only in the larger samples and meta\u2010analyses. In the largest cohort, we found indications that risk\u2010taking proneness mediated the association between<jats:italic>CADM2<\/jats:italic>and latent factors for lifetime smoking and regular alcohol use. This study extends earlier findings that<jats:italic>CADM2<\/jats:italic>plays a role in risky behaviors and self\u2010control. It also provides insight into gene\u2010level effect sizes and demonstrates the feasibility of testing mediation. These findings present a good starting point for investigating biological etiological pathways underlying risky behaviors.<\/jats:p>","DOI":"10.1111\/adb.13015","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T22:06:33Z","timestamp":1613858793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Associations between the<i>CADM2<\/i>gene, substance use, risky sexual behavior, and self\u2010control: A phenome\u2010wide association study"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6170-4018","authenticated-orcid":false,"given":"Rachel M.","family":"Arends","sequence":"first","affiliation":[{"name":"Department of Psychiatry Radboud University Medical Center The Netherlands"},{"name":"Donders Center for Medical Neuroscience Donders Institute for Brain, Cognition and Behavior The Netherlands"},{"name":"Tactus Addiction Care The 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