Genetically Informative Mediation Modeling Applied to Stressors and Personality-Disorder Traits in Etiology of Alcohol Use Disorder
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A statistical mediation model was developed within a twin design to investigate the etiology of alcohol use disorder (AUD). Unlike conventional statistical mediation models, this biometric mediation model can detect unobserved confounding. Using a sample of 1410 pairs of Norwegian twins, we investigated specific hypotheses that DSM-IV personality-disorder (PD) traits mediate effects of childhood stressful life events (SLEs) on AUD, and that adulthood SLEs mediate effects of PDs on AUD. Models including borderline PD traits indicated unobserved confounding in phenotypic path coefficients, whereas models including antisocial and impulsive traits did not. More than half of the observed effects of childhood SLEs on adulthood AUD were mediated by adulthood antisocial and impulsive traits. Effects of PD traits on AUD 5‒10 years later were direct rather than mediated by adulthood SLEs. The results and the general approach contribute to triangulation of developmental origins for complex behavioral disorders.
KeywordsStatistical mediation model Twin study Causality Stressful life events Antisocial personality disorder Borderline personality disorder Substance use
We acknowledge funding from the US National Institutes of Health and National Institute on Drug Abuse (1R01DA037558-01A1), the Research Council of Norway (226985 and 240061), the Norwegian Foundation for Health and Rehabilitation, the Norwegian Council for Mental Health, and the European Commission under the program “Quality of Life and Management of the Living Resources” of the Fifth Framework Program (QLG2-CT-2002-01254). TR had full access to all the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Compliance with ethical standards
Conflict of interest
Tom Rosenström, Nikolai Czajkowski, Eivind Ystrom, Robert Krueger, Steven Aggen, Nathan Gillespie, Espen Eilertsen, Ted Reichborn-Kjennerud, and Fartein Torvik declare that they have no conflict of interest.
Approval was received from The Norwegian Data Inspectorate and the Regional Committee for Medical and Health Research Ethics.
Human and animal rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
A written informed consent was obtained from all participants after a complete description of the study.
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