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| PMID |
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| TITLE |
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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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| ABSTRACT |
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| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| 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 |
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| AUTHORS |
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| 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 |
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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 |
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Netherlands Twin Register, The Netherlands. |
| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
|
Netherlands Twin Register, The Netherlands. |
| Schellekens AFA |
|
Schellekens |
Arnt F A |
AFA |
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Nijmegen Institute for Scientist-Practitioners in Addiction, The Netherlands. |
| Vink JM |
|
Vink |
Jacqueline M |
JM |
|
Behavioural Science Institute, Radboud University, The Netherlands. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: Addiction biology |
| ISOABBREVIATION: Addict Biol |
| YEAR: 2021 |
| MONTH: Feb |
| DAY: 18 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1369-1600 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Addict Biol |
| COUNTRY: United States |
| ISSNLINKING: 1355-6215 |
| NLMUNIQUEID: 9604935 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GRANTID |
AGENCY |
COUNTRY |
| APP1069141 |
National Health and Medical Research Council Project |
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|
Center for Tobacco Products of the U.S. Food and Drug Administration (FDA) |
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| U54DA036105 |
National Institute on Drug Abuse of the National Institutes of Health (NIH) |
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|
National Institutes of Health Roadmap for Medical Research |
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| UL1RR031990 |
NCRR NIH HHS |
United States |
| K01AA024152 |
NIAAA NIH HHS |
United States |
| P50 AA022537 |
NIAAA NIH HHS |
United States |
| K02AA018755 |
Virginia Commonwealth University |
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| R37AA011408 |
Virginia Commonwealth University |
|
| P20 AA017828 |
NIAAA NIH HHS |
United States |
|
Amsterdam Neuroscience |
|
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Foundation Volksbond Rotterdam |
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NINDS |
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NIMH |
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NIDA |
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NHLBI |
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NHGRI |
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NCI |
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Common Fund of the Office of the Director of the National Institutes of Health |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| CADM2 |
| multi-cohort |
| phenome-wide |
| risky behavior |
| self-control |
| substance use |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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