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Disentangling the influences of parental genetics on offspring's cognition, education, and psychopathology via genetic and phenotypic pathways

Axelrud, Luiza, Hoffmann, Mauricio, Vosberg, Daniel, Santoro, Marcos, Pan, Pedro, Gadelha, Ary, Belangero, Sinita, Euripedes, Miguel, Shin, Jean, Thapar, Anita ORCID:, Smoller, Jordan, Pausova, Zdenka, Rohde, Luis, Keller, Matthew, Paus, Tomas and Salum, Giovanni 2022. Disentangling the influences of parental genetics on offspring's cognition, education, and psychopathology via genetic and phenotypic pathways. Journal of Child Psychology and Psychiatry 64 (3) , pp. 408-416. 10.1111/jcpp.13708

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Background 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. Methods 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. Results 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. Conclusions 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Wiley
ISSN: 0021-9630
Date of First Compliant Deposit: 12 September 2022
Date of Acceptance: 24 August 2022
Last Modified: 02 Oct 2023 06:51

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