Associations between the CADM2 gene, substance use, risky sexual behavior, and self-control: A phenome-wide association study

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dc.authoridvan der Zee, Mattthijs/0000-0003-4076-9167
dc.authoridZietsch, Brendan/0000-0003-0274-6140
dc.authoridMitchell, Brittany/0000-0002-9050-1516
dc.authoridThomas, Nathaniel/0000-0001-6291-0518
dc.authoridHickie, Ian/0000-0001-8832-9895
dc.authoridDerks, Eske/0000-0002-6292-6883
dc.authoridGordon, Scott/0000-0001-7623-328X
dc.contributor.authorArends, Rachel M.
dc.contributor.authorPasman, Joelle A.
dc.contributor.authorVerweij, Karin J. H.
dc.contributor.authorDerks, Eske M.
dc.contributor.authorGordon, Scott D.
dc.contributor.authorHickie, Ian
dc.contributor.authorThomas, Nathaniel S.
dc.date.accessioned2024-09-29T16:04:33Z
dc.date.available2024-09-29T16:04:33Z
dc.date.issued2021
dc.departmentKarabük Üniversitesien_US
dc.description.abstractRisky behaviors, such as substance use and unprotected sex, are associated with various physical and mental health problems. Recent genome-wide association studies indicated that variation in the cell adhesion molecule 2 (CADM2) gene plays a role in risky behaviors and self-control. In this phenome-wide 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)-level and gene-level association tests within four samples (25 and Up, Spit for Science, Netherlands Twin Register, and UK Biobank and meta-analyses over all samples (combined sample of 362,018 participants) were conducted to test associations between CADM2, substance- and sex-related risk behaviors, and various measures related to self-control. We found significant associations between the CADM2 gene, various risky behaviors, and different measures of self-control. 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-analyses. In the largest cohort, we found indications that risk-taking proneness mediated the association between CADM2 and latent factors for lifetime smoking and regular alcohol use. This study extends earlier findings that CADM2 plays a role in risky behaviors and self-control. It also provides insight into gene-level effect sizes and demonstrates the feasibility of testing mediation. These findings present a good starting point for investigating biological etiological pathways underlying risky behaviors.en_US
dc.description.sponsorshipNational Health and Medical Research Council Project [APP1069141]; Center for Tobacco Products of the U.S. Food and Drug Administration (FDA); National Institute on Drug Abuse of the National Institutes of Health (NIH) [U54DA036105]; National Institutes of Health Roadmap for Medical Research; National Center for Research Resources [UL1RR031990]; National Institute on Alcohol Abuse and Alcoholism [K01AA024152]; Virginia Commonwealth University [P50 AA022537, K02AA018755, R37AA011408, P20 AA017828]; Foundation Volksbond Rotterdam; NINDS; NIMH; NIDA; NHLBI; NCI; Amsterdam Neuroscience; Common Fund of the Office of the Director of the National Institutes of Healthen_US
dc.description.sponsorshipNational Health and Medical Research Council Project, Grant/Award Number: APP1069141; Center for Tobacco Products of the U.S. Food and Drug Administration (FDA); National Institute on Drug Abuse of the National Institutes of Health (NIH), Grant/Award Number: U54DA036105; National Institutes of Health Roadmap for Medical Research; National Center for Research Resources, Grant/Award Number: UL1RR031990; National Institute on Alcohol Abuse and Alcoholism, Grant/Award Number: K01AA024152; Virginia Commonwealth University, Grant/Award Numbers: P50 AA022537, K02AA018755, R37AA011408, P20 AA017828; Amsterdam Neuroscience; Foundation Volksbond Rotterdam; NINDS; NIMH; NIDA; NHLBI; NHGRI; NCI; Common Fund of the Office of the Director of the National Institutes of Healthen_US
dc.identifier.doi10.1111/adb.13015
dc.identifier.issn1355-6215
dc.identifier.issn1369-1600
dc.identifier.issue6en_US
dc.identifier.pmid33604983en_US
dc.identifier.urihttps://doi.org/10.1111/adb.13015
dc.identifier.urihttps://hdl.handle.net/20.500.14619/6202
dc.identifier.volume26en_US
dc.identifier.wosWOS:000619310300001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofAddiction Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCADM2en_US
dc.subjectmulti? cohorten_US
dc.subjectphenome? wideen_US
dc.subjectrisky behavioren_US
dc.subjectself? controlen_US
dc.subjectsubstance useen_US
dc.titleAssociations between the CADM2 gene, substance use, risky sexual behavior, and self-control: A phenome-wide association studyen_US
dc.typeArticleen_US

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