Genetically Informative Mediation Modeling Applied to Stressors and Personality-Disorder Traits in Etiology of Alcohol Use Disorder.

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.