Axelrud Luiza K, Hoffmann Maurício S, Vosberg Daniel E, Santoro Marcos, Pan Pedro M, Gadelha Ary, Belangero Sintia I, Miguel Euripedes C, Shin Jean, Thapar Anita, Smoller Jordan W, Pausova Zdenka, Rohde Luis A, Keller Matthew C, Paus Tomáš, Salum Giovanni A
Section on Negative Affect and Social Processes, Department of Psychiatry and Legal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
National Institute of Developmental Psychiatry (INPD, CNPq), São Paulo, Brazil.
J Child Psychol Psychiatry. 2023 Mar;64(3):408-416. doi: 10.1111/jcpp.13708. Epub 2022 Sep 26.
Specific pathways of intergenerational transmission of behavioral traits remain unclear. Here, we aim to investigate how parental genetics influence offspring cognition, educational attainment, and psychopathology in youth.
Participants for the discovery sample were 2,189 offspring (aged 6-14 years), 1898 mothers and 1,017 fathers who underwent genotyping, psychiatric, and cognitive assessments. We calculated polygenic scores (PGS) for cognition, educational attainment, attention-deficit hyperactivity disorder (ADHD), and schizophrenia for the trios. Phenotypes studied included educational and cognitive measures, ADHD and psychotic symptoms. We used a stepwise approach and multiple mediation models to analyze the effect of parental PGS on offspring traits via offspring PGS and parental phenotype. Significant results were replicated in a sample of 1,029 adolescents, 363 mothers, and 307 fathers.
Maternal and paternal PGS for cognition influenced offspring general intelligence and executive function via offspring PGS (genetic pathway) and parental education (phenotypic pathway). Similar results were found for parental PGS for educational attainment and offspring reading and writing skills. These pathways fully explained associations between parental PGS and offspring phenotypes, without residual direct association. Associations with maternal, but not paternal, PGS were replicated. No associations were found between parental PGS for psychopathology and offspring specific symptoms.
Our findings indicate that parental genetics influences offspring cognition and educational attainment by genetic and phenotypic pathways, suggesting the expression of parental phenotypes partially explain the association between parental genetic risk and offspring outcomes. Multiple mediations might represent an effective approach to disentangle distinct pathways for intergenerational transmission of behavioral traits.
行为特征的代际传递的具体途径仍不清楚。在此，我们旨在研究父母的基因如何影响青少年后代的认知、教育程度和精神病理学。
发现样本的参与者包括2189名后代（6 - 14岁）、1898名母亲和1017名父亲，他们接受了基因分型、精神病学和认知评估。我们计算了三人组的认知、教育程度、注意力缺陷多动障碍（ADHD）和精神分裂症的多基因评分（PGS）。所研究的表型包括教育和认知指标、ADHD和精神病症状。我们采用逐步方法和多重中介模型，通过后代PGS和父母表型来分析父母PGS对后代特征的影响。在1029名青少年、363名母亲和307名父亲的样本中重复了显著结果。
父母的认知PGS通过后代PGS（遗传途径）和父母教育（表型途径）影响后代的一般智力和执行功能。父母的教育程度PGS和后代的读写技能也有类似结果。这些途径完全解释了父母PGS与后代表型之间的关联，没有残留的直接关联。与母亲PGS的关联得到了重复，但与父亲PGS的关联未得到重复。未发现父母的精神病理学PGS与后代特定症状之间存在关联。
我们的研究结果表明，父母基因通过遗传和表型途径影响后代的认知和教育程度，这表明父母表型的表达部分解释了父母遗传风险与后代结果之间的关联。多重中介可能是一种有效的方法，用于理清行为特征代际传递的不同途径。
