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We performed genome-wide association studies (GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale (<jats:italic>N<\/jats:italic>\u2009=\u2009123,509\u2013133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation (<jats:italic>N<\/jats:italic>\u2009=\u2009130,684). Because these GWAS implicated the gene <jats:italic>CADM2<\/jats:italic>, we next performed single-SNP phenome-wide studies (PheWAS) of several of the implicated variants in <jats:italic>CADM2<\/jats:italic> in a multi-ancestral 23andMe cohort (<jats:italic>N<\/jats:italic>\u2009=\u20093,229,317, European; <jats:italic>N<\/jats:italic>\u2009=\u2009579,623, Latin American; <jats:italic>N<\/jats:italic>\u2009=\u2009199,663, African American). Finally, we produced <jats:italic>Cadm2<\/jats:italic> mutant mice and used them to perform a Mouse-PheWAS (\u201cMouseWAS\u201d) by testing them with a battery of relevant behavioral tasks. In humans, impulsive personality traits showed modest chip-heritability (~6\u201311%), and moderate genetic correlations (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>g<\/jats:italic><\/jats:sub>\u2009=\u20090.20\u20130.50) with other personality traits, and various psychiatric and medical traits. We identified significant associations proximal to genes such as <jats:italic>TCF4<\/jats:italic> and <jats:italic>PTPRF<\/jats:italic>, and also identified nominal associations proximal to <jats:italic>DRD2<\/jats:italic> and <jats:italic>CRHR1<\/jats:italic>. PheWAS for <jats:italic>CADM2<\/jats:italic> variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. Our results further delineate the role of <jats:italic>CADM2<\/jats:italic> in impulsivity and numerous other psychiatric and somatic traits across ancestries and species.<\/jats:p>","DOI":"10.1038\/s41398-023-02453-y","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T18:02:27Z","timestamp":1683914547000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-5699","authenticated-orcid":false,"given":"Sandra","family":"Sanchez-Roige","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela V.","family":"Jennings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley H. 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SBB was also supported by P50DA037844, SSR was also supported by NIH\/NIDA DP1DA054394. JM and SSR were supported by the Brain and Behavior Foundation (grant 27676) and the Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. SAB was supported by NIH\/NIMH grants R01MH108653 and R21MH117518. AMBL was supported by NIH\/NIAAA grant K99AA027835. TB acknowledges support by NIH\/NIDA R01 DA018928. JM is supported by the Peter Boris Chair in Addictions Research. HHAT is funded through a Natural Science and Engineering Research Council PGS-D scholarship, and studies in Cohort 2 were supported by the Canadian Institutes of Health Research Project Grant (PJT-173442 to JYK). PF and SLE are employees of 23andMe, Inc., and hold stock or stock options in 23andMe. JY reports having received grant support funding from Sunovion, Heptares, and Gilgamesh, as well as honoraria from Marvel Biotech, none of which were involved in the current project. The other authors report no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"167"}}