Evidence for Genetic Nurture Effects on Substance Use.

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 effects on tobacco, alcohol and cannabis use in up to 15,863 adults with at least one genotyped parent from the Lifelines cohort. Genetic nurture significantly influenced smoking quantity (cigarettes per day: =0.03; pack-years: =0.02), accounting for 18.8% and 28.6% of the corresponding effects of genetic transmission. However, it had minimal impact on tobacco or cannabis initiation, suggesting a stage-specific pattern. Maternal and paternal genetic nurture contributed equally to offspring smoking quantity, especially for pack-years. Mediation analyses revealed that both maternal and paternal smoking partially explained these effects, with higher mediation proportions observed for maternal smoking quantity. These findings highlight the importance of considering stage-specific and parent-specific effects when investigating genetic nurture in substance use.