Estimating the impact of transmitted and non-transmitted psychiatric and neurodevelopmental polygenic scores on youth emotional problems

Shakeshaft, Amy ORCID: https://orcid.org/0000-0003-1412-5413, Martin, Joanna ORCID: https://orcid.org/0000-0002-8911-3479, Dennison, Charlotte A. ORCID: https://orcid.org/0000-0002-7493-2041, Riglin, Lucy, Lewis, Cathryn M., O'Donovan, Michael ORCID: https://orcid.org/0000-0001-7073-2379 and Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X 2023. Estimating the impact of transmitted and non-transmitted psychiatric and neurodevelopmental polygenic scores on youth emotional problems. Molecular Psychiatry 10.1038/s41380-023-02319-1

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Abstract

Anxiety and depression (emotional disorders) are familial and heritable, especially when onset is early. However, other cross-generational studies suggest transmission of youth emotional problems is explained by mainly environmental risks. We set out to test the contribution of parental non-transmitted genetic liability, as indexed by psychiatric/neurodevelopmental common polygenic liability, to youth emotional problems using a UK population-based cohort: the Millennium Cohort Study. European (N = 6328) and South Asian (N = 814) ancestries were included, as well as a subset with genomic data from both parents (European: N = 2809; South Asian: N = 254). We examined the association of transmitted (PGST) and non-transmitted polygenic scores (PGSNT) for anxiety, depression, bipolar disorder and neurodevelopmental disorders (attention-deficit/hyperactivity disorder [ADHD], autism spectrum disorder [ASD], schizophrenia) with youth emotional disorder and symptom scores, measured using the parent- and self-reported Strengths and Difficulties Questionnaire emotional subscale at 6 timepoints between ages 3–17 years. In the European sample, PGST for anxiety and depression, but not bipolar disorder, were associated with emotional disorder and symptom scores across all ages, except age 3, with strongest association in adolescence. ADHD and ASD PGST also showed association across ages 11–17 years. In the South Asian sample, evidence for associations between all PGST and outcome measures were weaker. There was weak evidence of association between PGSNT for anxiety and depression and age 17 symptom scores in the South Asian sample, but not in the European sample for any outcome. Overall, PGST for depression, anxiety, ADHD and ASD contributed to youth emotional problems, with stronger associations in adolescence. There was limited support for non-transmitted genetic effects: these findings do not support the hypothesis that parental polygenic psychiatric/neurodevelopmental liability confer risk to offspring emotional problems through non-transmitted rearing/nurture effects.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	1359-4184
Date of First Compliant Deposit:	14 November 2023
Date of Acceptance:	6 November 2023
Last Modified:	17 Jan 2024 02:23
URI:	https://orca.cardiff.ac.uk/id/eprint/163908

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