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

Abstract

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.

Mental Health Disparities Mediating Increased Risky Sexual Behavior in Sexual Minorities: A Twin Approach

“…In the next model (Genetic model 3), causal paths, factor-specific, and variable-specific ACE components were specified to test whether this was a more parsimonious description of the factor covariances. 2 A better fit of the second model would indicate that the covariances of the three latent factors were more consistent with shared effects of common A , C , and E factors (i.e., including pleiotropy), while a better fit of the third model would indicate a combination of causal effects and transmitted component effects through the causal paths giving a more parsimonious explanation of the factor relationships (Rosenström et al, 2019 ). Sex differences were tested in the final model by alternately constraining factor-specific component loadings and the causal path coefficients to be equal in male and female twins.…”

Do psychosocial factors mediate sexual minorities’ risky sexual behaviour? A twin study.

“…The second model, the common-factor independent pathway model (CFIP, Genetic Model 2; online Supplemental Materials Figure S2b) tested whether the factor relationships were completely due to pleiotropic genetic and environmental effects without mediation paths. In the third model, the biometric mediation model (Genetic Model 3; Figure 2), ACE components and mediation paths were specified; allowing comparison with other genetic models to test for confounding of the mediation paths by ACE influences (Rosenström et al, 2019). Model selection for best fit for nested models was based on likelihood ratio testing using chi squared values and degrees of freedom while Akaike's information criterion (AIC) and Bayesian information criterion (BIC) were used for nonnested models (Kline, 2016).…”

Future directions in personality pathology

“…Studies of families and twins tend to show that genetic risk is not specific to particular disorders, but is largely a transdiagnostic vulnerability factor [21][22][23][24]. In terms of etiology, twin studies show that genetic and environmental effects on a general factor appear to be roughly equal [25,26]. In family studies, increased relatedness is associated with a general increase in risk of mental disorder, given a diagnosis of severe mental disorder in a proband (e.g.…”