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

ABSTRACT: Risky 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.

SUBMITTER: Arends RM

PROVIDER: S-EPMC8596397 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionJustice-involved adolescents are at high risk for sexually transmitted infections; one primary reason is co-occurring substance use. This study investigates the additive benefit of including alcohol and cannabis use content in a theory-based sexual risk reduction intervention, delivered using group-based motivational enhancement therapy.Study designThis study had a cluster randomized design, with randomization of single-sex clusters to 1 of 3 interventions.Setting/participantsParticipants were male and female justice-involved adolescents (N=460) residing in youth detention facilities. Data were collected from 2010 to 2014; analyses were completed in 2018-2019.InterventionAdolescents were randomized to 1 of 3 motivational enhancement therapy interventions: sexual risk reduction intervention, sexual risk reduction intervention with alcohol content, or sexual risk reduction intervention with alcohol and cannabis content.Main outcome measuresThe primary outcome was risky sexual behavior (aggregation of condom use and frequency of intercourse), measured every 3 months for 1 year. Secondary outcomes were theoretical mechanisms on which the intervention was based (condom use attitudes, self-efficacy, peer norms, and behavioral intentions), collected at baseline and post-test.ResultsRisky sexual behavior significantly decreased from baseline to 3-month follow-up (t=10.59, p<0.001) and this decrease was maintained 1 year later (t=9.04, p<0.001). Intervention was associated with improved values on all theoretical mechanisms. Although all outcomes improved over time, changes did not differ by intervention condition (p>0.29 for all). Comparisons to a historical, information-only, sexual risk reduction control arm conducted with a similar juvenile justice sample confirm the effectiveness of all 3 motivational enhancement therapy-based interventions.ConclusionsAll 3 interventions were associated with decreased sexual risk up to 1 year later, suggesting that the intervention modality (motivational enhancement therapy) may resonate with this population beyond the specific substance use content. This single-session manualized intervention can be readily disseminated to juvenile justice settings.Trial registrationThis study is registered at www.clinicaltrials.gov NCT01170260.

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

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