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 utilizes 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 influences cigarettes per day (CPD, β = 0.037, p FDR = 0.020) and pack-years ( β = 0.028, p FDR = 0.035), accounting for 22–26% of direct genetic transmission effects. Longitudinal analysis reveals that genetic nurture on current CPD persists across adulthood, whereas direct genetic transmission effects attenuate with age. Maternal and paternal genetic nurture are similar in magnitude. Mediation analyses indicate that genetic nurture partially operates 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.