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A multivariate approach to understanding the genetic overlap between externalizing phenotypes and substance use
Holly E Poore1, Alexander Hatoum2, Travis T Mallard3
1Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, USA.
Addiction Biology
|August 30, 2023
Summary
Genetic risk for substance use disorders (SUDs) and externalizing behaviors largely overlaps, indicating shared genetic influences. However, both also possess unique genetic variance, offering insights for future research.
Area of Science:
- Behavioral Genetics
- Psychiatric Genetics
- Quantitative Genetics
Background:
- Substance use disorders (SUDs) and externalizing phenotypes share phenotypic and genetic correlations.
- Understanding the shared genetic architecture is crucial for identifying underlying biological mechanisms.
Purpose of the Study:
- To explore the shared genetic architecture among six externalizing phenotypes and four SUDs.
- To investigate genetic correlations between identified factors and other psychological traits.
- To quantify the polygenic overlap between externalizing and addiction risk.
Main Methods:
- Genomic structural equation modeling was employed.
- Confirmatory factor analytic models (common factor, two-factor, bifactor) were evaluated.
- Genetic correlations and polygenic overlap (MiXeR) were analyzed.
Main Results:
- Common and two-factor models best fit the data, demonstrating good reliability.
- High genetic correlations were observed between externalizing and addiction risk factors (rg ≥ 0.87).
- MiXeR indicated substantial shared genetic variants (81% from externalizing to addiction, 56% from addiction to externalizing).
Conclusions:
- Externalizing behaviors and addiction genetic risk are largely shared.
- Both constructs retain meaningful unique genetic variance.
- Findings can guide future research into specific genetic influences on SUDs and externalizing traits.
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