Hicks, B. M. | bioRxiv Science

bioRxiv2020

Polygenic Risk Score for Smoking is associated with Externalizing Psychopathology and Disinhibited Personality Traits but not Internalizing Psychopathology in Adolescence

ImportanceLarge consortia of genome wide association studies have yielded more accurate polygenic risk scores (PRS) that aggregate the small effects of many genetic variants to characterize the genetic architecture of disorders and provide a personalized measure of genetic risk. ObjectiveWe examined whether a PRS for smoking measured genetic risk for general behavioral disinhibition by estimating its associations with externalizing and internalizing psychopathology and related personality traits. We examined these associations at multiple time points in adolescence using more refined phenotypes defined by stable characteristics across time and at young ages, which reduced potential confounds associated with cumulative exposure to substances and reverse causality. MethodsRandom intercept panel models were fit to symptoms of conduct disorder, oppositional defiant disorder, major depressive disorder (MDD), and teacher ratings of externalizing and internalizing problems and personality traits at ages 11, 14, and 17 years-old in the Minnesota Twin Family Study (N = 3225). ResultsThe smoking PRS had strong associations with the random intercept factors for all the externalizing measures (mean standardized {beta} = .27), agreeableness ({beta}=-.22, 95% CI: -.28, -.16), and conscientiousness ({beta}=-.19, 95% CI: -.24, -.13), but was not significantly associated with the internalizing measures (mean {beta} = .06) or extraversion ({beta}=.01, 95% CI: -.05, .07). After controlling for smoking at age 17, the associations with the externalizing measures (mean {beta} = .13) and personality traits related to behavioral control (mean {beta} = -.10) remained statistically significant. Conclusions and RelevanceThe smoking PRS measures genetic influences that contribute to a spectrum of phenotypes related to behavioral disinhibition including externalizing psychopathology and normal-range personality traits related to behavioral control, but not internalizing psychopathology. Continuing to identify the correlates and delineate the mechanisms of the genetic influences associated with disinhibition could have substantial impact in mitigating a variety of public health problems (e.g., mental health, academic achievement, criminality). Key PointsO_ST_ABSQuestionC_ST_ABSDoes a polygenic risk scores (PRS) for smoking measure genetic risk for behavioral disinhibition in general? FindingsThe smoking PRS was associated with externalizing psychopathology and personality traits related to behavioral control, but not internalizing psychopathology and extraversion during adolescence, even after controlling for smoking status. MeaningThe smoking PRS measures genetic influences on behavioral disinhibition in general which is associated with a variety of important outcomes including mental health, academic success, and criminality.

genetics↗

bioRxiv2020

Polygenic Risk Scores Predict the Development of Alcohol and Nicotine Use Problems from Adolescence through Young Adulthood

ObjectiveMolecular genetic studies of alcohol and nicotine have identified many genome-wide loci. We examined the predictive utility of drinking and smoking polygenic scores (PGS) for alcohol and nicotine use from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied between consumption versus pathological use. MethodsLatent growth curve models with structured residuals were used to assess the predictive utility of drinks per week and regular smoking PGS for measures of alcohol and nicotine consumption and problematic use from age 14 to 34. PGSs were generated from the largest discovery sample for alcohol and nicotine use to date (i.e., GSCAN), and examined for associations with alcohol and nicotine use in the Minnesota Twin Family Study (N=3225). ResultsThe drinking PGS was a significant predictor of age 14 problematic alcohol use and increases in problematic use during young adulthood. The smoking PGS was a significant predictor for all nicotine use outcomes. After adjusting for the effects of both PGSs, the smoking PGS demonstrated incremental predictive utility for most alcohol use outcomes and remained a significant predictor of nicotine use trajectories. ConclusionsHigher PGS for drinking and smoking were associated with more problematic levels of substance use longitudinally. The smoking PGS seems to capture both nicotine-specific and non-specific genetic liability for substance use, and may index genetic risk for broader externalizing behavior. Validation of PGS within longitudinal designs may have important clinical implications should future studies support the clinical utility of PGS for substance use disorders.

genetics↗