Genetic Nurture in Intergenerational Transmission of Substance Use

Abstract

Substance use runs in families. Beyond genetic transmission, parental genetics can indirectly influence offspring substance use through the rearing environment, known as "genetic nurture". This study utilized transmitted and non-transmitted polygenic scores to investigate genetic nurture on tobacco, alcohol, and cannabis use in up to 15,863 adults with at least one genotyped parent from Lifelines, a population-based cohort study. Genetic nurture significantly influenced cigarettes per day (CPD, {beta}=.037, pFDR=.020) and pack-years ({beta}=.028, pFDR =.035), accounting for 22-26% of direct genetic transmission effects. Longitudinal analysis revealed that genetic nurture on current CPD persisted across adulthood, whereas direct genetic transmission effects attenuated with age. Maternal and paternal genetic nurture were similar in magnitude. Mediation analyses indicated that genetic nurture partially operated through both parents smoking quantity, with a stronger mediated effect through maternal smoking, particularly among daughters. These findings highlight genetic nurture as a persistent mechanism in the intergenerational transmission of smoking, operating through parental smoking behaviors.