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How important are parents in the development of child anxiety and depression? A genomic analysis of parent-offspring trios in the Norwegian Mother Father and Child Cohort Study (MoBa)

By Rosa Cheesman, Espen Moen Eilertsen, Yasmin I Ahmadzadeh, Line C Gjerde, Laurie J Hannigan, Alexandra Havdahl, Alexander I Young, Thalia C. Eley, Pål R. Njølstad, Per Minor Magnus, Ole A Andreassen, Eivind Ystrom, Tom A McAdams

Posted 17 Apr 2020
medRxiv DOI: 10.1101/2020.04.14.20064782

Background: Many studies detect associations between parent behaviour and child symptoms of anxiety and depression. However, most do not account for shared genetic risk. Quantitative genetic designs provide a means of controlling for shared genes, but rely on observed putative exposure variables, and require data from highly specific family structures. Methods: The intergenerational genomic method, Relatedness Disequilibrium Regression (RDR), indexes environmental effects of parents on child traits using measured genotypes. RDR estimates how much the parent genome influences the child indirectly via the environment, over and above effects of genes acting directly in the child. This "genetic nurture" effect is agnostic to parent phenotype and captures unmeasured heritable parent behaviours. We applied RDR in a sample of 11,598 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) to estimate parental genetic nurture separately from direct child genetic effects on anxiety and depression symptoms at age 8. We also tested for mediation of genetic nurture via maternal emotional symptoms. Results were compared to a complementary non-genomic pedigree model. Results: Parental genetic nurture significantly influenced depression symptoms at age 8, explaining 14% of the phenotypic variance. Subsequent analyses suggested that maternal anxiety and depression partially mediated the parental genetic nurture effect. The genetic nurture effect was mirrored by the finding of shared family environmental influence in our complementary pedigree model. In contrast, variance in anxiety symptoms was not significantly influenced by common genetic variation in children or parents, despite a moderate pedigree heritability. Conclusions: Genomic methods like RDR represent new opportunities for genetically sensitive family research in humans, which until now has been largely confined to adoption, twin and other pedigree designs. Our results are relevant to debates about the role of parents in the development of emotional problems in children, and possibly where to intervene to reduce problems.

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