Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
33604983
TITLE
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.
2021 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.
DATE PUBLISHED
2021 Feb 18
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2020/03/20
revised 2020/11/05
accepted 2021/01/15
entrez 2021/02/19 06:14
pubmed 2021/02/20 06:00
medline 2021/02/20 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Arends RM Arends Rachel M RM Tactus Addiction Care, The Netherlands.
Pasman JA Pasman Joëlle A JA Behavioural Science Institute, Radboud University, The Netherlands.
Verweij KJH Verweij Karin J H KJH Faculty of Medicine, Amsterdam Medical Centre and University of Amsterdam, The Netherlands.
Derks EM Derks Eske M EM Genetic Epidemiology, Statistical Genetics and Translational Neurogenomics Laboratories, QIMR Berghofer Medical Research Institute, Australia.
Gordon SD Gordon Scott D SD Genetic Epidemiology, Statistical Genetics and Translational Neurogenomics Laboratories, QIMR Berghofer Medical Research Institute, Australia.
Hickie I Hickie Ian I Brain and Mind Centre, University of Sydney, Australia.
Thomas NS Thomas Nathaniel S NS Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
Aliev F Aliev Fazil F Department of African American Studies, Virginia Commonwealth University, Richmond, VA, USA.
Zietsch BP Zietsch Brendan P BP School of Medicine and School of Psychology, University of Queensland, Australia.
van der Zee MD van der Zee Matthijs D MD Netherlands Twin Register, The Netherlands.
Mitchell BL Mitchell Brittany L BL School of Biomedical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia.
Martin NG Martin Nicholas G NG School of Medicine and School of Psychology, University of Queensland, Australia.
Dick DM Dick Danielle M DM Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
Gillespie NA Gillespie Nathan A NA Virginia Institute for Psychiatric and Behavior Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
de Geus EJC de Geus Eco J C EJC Netherlands Twin Register, The Netherlands.
Boomsma DI Boomsma Dorret I DI Netherlands Twin Register, The Netherlands.
Schellekens AFA Schellekens Arnt F A AFA Nijmegen Institute for Scientist-Practitioners in Addiction, The Netherlands.
Vink JM Vink Jacqueline M JM Behavioural Science Institute, Radboud University, The Netherlands.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Addiction biology
ISOABBREVIATION: Addict Biol
YEAR: 2021
MONTH: Feb
DAY: 18
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1369-1600
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Addict Biol
COUNTRY: United States
ISSNLINKING: 1355-6215
NLMUNIQUEID: 9604935
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
APP1069141 National Health and Medical Research Council Project
Center for Tobacco Products of the U.S. Food and Drug Administration (FDA)
U54DA036105 National Institute on Drug Abuse of the National Institutes of Health (NIH)
National Institutes of Health Roadmap for Medical Research
UL1RR031990 NCRR NIH HHS United States
K01AA024152 NIAAA NIH HHS United States
P50 AA022537 NIAAA NIH HHS United States
K02AA018755 Virginia Commonwealth University
R37AA011408 Virginia Commonwealth University
P20 AA017828 NIAAA NIH HHS United States
Amsterdam Neuroscience
Foundation Volksbond Rotterdam
NINDS
NIMH
NIDA
NHLBI
NHGRI
NCI
Common Fund of the Office of the Director of the National Institutes of Health
GENERAL NOTE
KEYWORDS
KEYWORD
CADM2
multi-cohort
phenome-wide
risky behavior
self-control
substance use
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's