Associations between the CADM2 gene, substance use, risky sexual behavior, and self-control: A phenome-wide association study.
paper
Cited
Public
- Authors
- Arends, Rachel M; Pasman, Joëlle A; Verweij, Karin J H; Derks, Eske M; Gordon, Scott D; Hickie, Ian; Thomas, Nathaniel S; Aliev, Fazil; Zietsch, Brendan P; van der Zee, Matthijs D; Mitchell, Brittany L; Martin, Nicholas G; Dick, Danielle M; Gillespie, Nathan A; de Geus, Eco J C; Boomsma, Dorret I; Schellekens, Arnt F A; Vink, Jacqueline M
- Year
- 2021
- Journal
- Addiction biology
- PMID
- 33604983
- DOI
- 10.1111/adb.13015
- PMCID
- PMC8596397
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.
Significance of associations between CADM2 and risk behavior factors, with and without a mediating effect of risk‐taking proneness. Path a: the effect of the predictor (CADM2) on the mediator (risk‐taking proneness); path b: the effect of the mediator on the outcome factors (tobacco (ab)use, lifetime smoking, and risky alcohol use); path c: the effect of the predictor on the outcome variables; path c': the effect of the predictor on the outcome variables controlling for the mediator. † C′ paths with attenuated p‐values, indicating a partial mediation effect
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Parsing genetically influenced risk pathways: genetic loci impact problematic alcohol use via externalizing and specific risk. | 2022 | 36180423 |
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