Mechanisms of Parent-Child Transmission of Tobacco and Alcohol Use with Polygenic Risk Scores: Evidence for a Genetic Nurture Effect

Parent-child similarity is a function of genetic and environmental transmission. In addition, genetic effects not transmitted to offspring may drive parental behavior, thereby affecting the rearing environment of the child. Measuring genetic proclivity directly, through polygenic risk scores (PRSs), provides a way to test for the effect of nontransmitted parental genotype, on offspring outcome, termed a "genetic nurture" effect--in other words, if and how parental genomes might affect their children through the environment. The current study used polygenic risk scores for smoking initiation, cigarettes per day, and drinks per week to predict substance use in a sample of 3,008 twins, assessed prospectively from age 17-29, and their parents, from the Minnesota Center for Twin and Family Research. Mixed-effects models were used to test for a genetic nurture effect whereby parental PRSs predict offspring tobacco and alcohol use after statistically adjusting for offspring's own PRS. Parental smoking initiation PRS predicted offspring cigarettes per day at age 24 ([beta] = 0.103, 95% CI [0.03, 0.17]) and alcohol use at age 17 ([beta] = 0.091, 95% CI [0.04, 0.14]) independent of shared genetics. There was also a suggestive independent association between the parent PRS and offspring smoking at age 17 ([beta] = 0.096; 95% CI [0.02, 0.17]). Mediation analyses provided some evidence for environmental effects of parental smoking, alcohol use, and family socioeconomic status. These findings, and more broadly the molecular genetic method used, have implications on the identification of environmental effects on developmental outcomes such as substance use. [The article was co-written with the GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN).]