Externalizing as a common genetic influence for a broad spectrum of substance use and behavioral conditions: A developmental perspective from the Avon Longitudinal Study of Parents and Children.
Background and aims: Recent large studies have established the genetic basis of several conceptually linked phenotypes of externalizing. Polygenic risk scores (PRSs) for these constructs are associated with a range of substance use and mental disorder phenotypes but have not been examined with both...
| Publicado en: | Addiction Vol. 120; no. 12; pp. 2559 - 2573 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=189104081&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 189104081 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09652140 AIO jtl: Addiction issn: 09652140 maglogo: Y pubinfo: dt: Dec2025 vid: 120 iid: 12 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 189104081 187133912 189104081 189104081 10.1111/add.70163 189104081 ppf: 2559 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Externalizing as a common genetic influence for a broad spectrum of substance use and behavioral conditions: A developmental perspective from the Avon Longitudinal Study of Parents and Children. aug: au: Deng, Wei Q. Belisario, Kyla Doggett, Amanda Pigeyre, Marie Pare, Guillaume Munafò, Marcus R. MacKillop, James affil: Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, Canada sug: subj: Externalizing Behavior Substance Use Disorders Familial and Genetic Parental Attitudes Genetic Risk Score Phenotype Gambling Familial and Genetic Internet Utilization Eating Behavior Behavior, Addictive Aging Human Prospective Studies Linear Regression Funding Source Questionnaires Data Analysis Software Descriptive Statistics Sensitivity and Specificity United Kingdom Sequence Analysis Male Female Adolescence Adult Disease Susceptibility Comparative Studies Adolescent: 13-18 years Adult: 19-44 years Male Female ab: Background and aims: Recent large studies have established the genetic basis of several conceptually linked phenotypes of externalizing. Polygenic risk scores (PRSs) for these constructs are associated with a range of substance use and mental disorder phenotypes but have not been examined with both pharmacological and non‐pharmacological addictive behaviors, or across a developmental window. This study identified biological pathways responsible for observed associations between PRSs and addiction phenotypes. Design, setting, participants: We selected genome‐wide association studies of 22 phenotypes, including substance use, general factors of externalizing and addiction, impulsivity and psychiatric conditions. Using summary statistics, we constructed PRSs in the offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) (nmax = 4995). Participants were genetically confirmed to be unrelated and of European‐like genetic similarity. Measurements: We examined the associations between PRSs and addiction‐related phenotypes including substance use, gambling, eating behaviors and internet use across different life stages, from adolescence to young adulthood. PRSs were partitioned by biological pathways to examine the common and unique mechanisms underlying the genetics of addiction‐related phenotypes. Findings The PRS of externalizing factor (PRSEXT) showed the strongest association across phenotypes for substance use (minP = 2.6 × 10‐31, adjusted R2 = 0.10–4.72%), gambling (minP = 1.0 × 10‐9, adjusted R2 = 0.18–1.50%), eating behaviors (minP = 8.2 × 10‐4, adjusted R2 = 0.11–0.65%) and internet use (minP = 1.4 × 10‐7, adjusted R2 = 0.17–1.04%). Sensitivity analyses excluding a small subset of ALSPAC participants who also contributed to the externalizing summary statistics, yielded consistent association effect sizes (R2 = 0.98), suggesting minimal bias. The results also revealed several time‐varying associations between several PRSs and addiction phenotypes. Notably, the genetic influence of externalizing factor on alcohol and tobacco use was significantly stronger at younger ages. Finally, we identified multiple biological pathways that contribute to the link between addiction‐related phenotypes and PRSEXT, emphasizing the importance of synaptic functions and neuronal plasticity in the context of gambling and substance use. Conclusions: There appears to be genetic evidence implicating externalizing as a common mechanism of substance and behavioral addictive behaviors. These results support the shared genetic liability across substance misuse, problematic gambling and internet use, and demonstrate the potential utility of externalizing traits as a transdiagnostic dimension across diverse forms of psychopathology. Notably, the predictive power of externalizing genetic liability appears developmentally dynamic, supporting the view that externalizing represents a broad, non‐time‐invariant risk factor that may give way to more specific disorder‐related influences over time. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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