부산대학교 도서관

Keywords: Genetics; gene-environment correlation; intergenerational transmission; cognition; educational attainment; polygenic scores 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 6-14years), 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. Article Note: Conflict of interest statement: See Acknowledgements for full disclosures. CAPTION(S): Appendix S1. Polygenic score calculation. Appendix S2. Offspring phenotypic measures. Appendix S3. Resplication sample. Table S1. Examples of predictive power for different PGS in mental health sciences. Table S2. Results for separate regressions for the discovery sample. Table S3. Results for multiple mediation adjusting for collider bias (other parent PGS) for the discovery sample. Table S4. Results for multiple mediation adjusting for assortative mating (i.e. other parent phenotype) for the discovery sample. Table S5. Results for multiple mediation adjusting for collider bias (other parent PGS) for the replication sample. Table S6. Results for multiple mediation adjusting for assortative mating (i.e. other parent phenotype) for the replication sample. Table S7. Results for the multiple mediations analyses testing pleiotropic effects. Table S8. Moderated mediations testing the effect of age ([less than or equal to]10years vs. >10years) on both genetic and phenotypic pathways for the associations between maternal PGS for educational attainment and offspring reading and writing. Table S9. Results for separate regressions for psychopathology. Byline: Luiza K. Axelrud, Maurício S. Hoffmann, Daniel E. Vosberg, Marcos Santoro, Pedro M. Pan, Ary Gadelha, Sintia I. Belangero, Euripedes C. Miguel, Jean Shin, Anita Thapar, Jordan W. Smoller, Zdenka Pausova, Luis A. Rohde, Matthew C. Keller, TomáÅ¡ Paus, Giovanni A. Salum