Luo Mannan, Trindade Pons Victória, Gillespie Nathan A, van Loo Hanna M
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
medRxiv. 2025 Aug 29:2025.08.28.25334658. doi: 10.1101/2025.08.28.25334658.
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.
物质使用在家族中具有遗传性。除了基因传递外，父母的基因还可通过养育环境间接影响后代的物质使用，这被称为“基因养育”。本研究利用传递和未传递的多基因分数，在来自生命线队列的多达15863名至少有一位基因分型父母的成年人中，研究基因养育对烟草、酒精和大麻使用的影响。基因养育显著影响吸烟量（每天吸烟支数：β = 0.03；吸烟包年数：β = 0.02），分别占基因传递相应影响的18.8%和28.6%。然而，它对烟草或大麻的开始使用影响极小，表明存在阶段特异性模式。母系和父系基因养育对后代吸烟量的贡献相同，尤其是对吸烟包年数。中介分析表明，母系和父系吸烟都部分解释了这些影响，母系吸烟量的中介比例更高。这些发现凸显了在研究物质使用中的基因养育时，考虑阶段特异性和父母特异性影响的重要性。
