Hagenbeek Fiona A, Pool René, Van Asselt Austin J, Ehli Erik A, Smit August B, Bartels Meike, Hottenga Jouke Jan, Dolan Conor V, van Dongen Jenny, Boomsma Dorret I
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Amsterdam Public Health (APH) research institute, Amsterdam, The Netherlands.
Mol Psychiatry. 2025 Apr 3. doi: 10.1038/s41380-025-02981-7.
The genetic makeup of parents can directly or indirectly affect their offspring phenome through genetic transmission or via the environment that is influenced by parental heritable traits. Our understanding of the mechanisms by which indirect genetic effects operate is limited. Here, we hypothesize that one mechanism is via the offspring methylome. To test this hypothesis, polygenic scores (PGSs) for schizophrenia, smoking initiation, educational attainment (EA), social deprivation, body mass index (BMI), and height were analyzed in a cohort of 1528 offspring and their parents (51.5% boys, mean [SD] age = 10 [2.8] years). We modelled parent and offspring PGSs on offspring buccal-DNA methylation, accounting for the own PGS of offspring, and found significant associations between parental PGSs for schizophrenia, EA, BMI, and height, and offspring buccal methylation sites, comprising 16, 2, 1, and 6 sites, respectively (alpha = 2.7 × 10). More DNA methylation sites were associated with maternal than paternal PGSs, possibly reflecting the maternal pre- and periconceptional environment or stronger maternal involvement in shaping the offspring's environment during early childhood.
父母的基因组成可通过基因传递或受父母可遗传性状影响的环境直接或间接地影响其后代的表现型组。我们对间接遗传效应发挥作用的机制的理解有限。在此，我们假设一种机制是通过后代的甲基化组。为了验证这一假设，我们在一个由1528名后代及其父母（51.5%为男孩，平均[标准差]年龄 = 10 [2.8]岁）组成的队列中分析了精神分裂症、开始吸烟、受教育程度（EA）、社会剥夺、体重指数（BMI）和身高的多基因评分（PGS）。我们根据后代口腔DNA甲基化对父母和后代的PGS进行建模，同时考虑后代自身的PGS，结果发现精神分裂症、EA、BMI和身高的父母PGS与后代口腔甲基化位点之间存在显著关联，分别包括16个、2个、1个和6个位点（α = 2.7×10）。与父本PGS相比，与母本PGS相关的DNA甲基化位点更多，这可能反映了母亲受孕前和受孕期间的环境，或者母亲在幼儿期对塑造后代环境的更强参与。
