Early manifestations of neurodevelopmental copy number variants in children: A population-based investigation

Dennison, Charlotte A. ORCID: https://orcid.org/0000-0002-7493-2041, Martin, Joanna ORCID: https://orcid.org/0000-0002-8911-3479, Shakeshaft, Amy ORCID: https://orcid.org/0000-0003-1412-5413, Riglin, Lucy, Powell, Victoria, Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862, O'Donovan, Michael C. ORCID: https://orcid.org/0000-0001-7073-2379 and Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X 2025. Early manifestations of neurodevelopmental copy number variants in children: A population-based investigation. Biological Psychiatry 10.1016/j.biopsych.2025.03.004

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Abstract

Background There is clinical interest in recognising copy number variants (CNVs) in children as many have immediate and long-term health implications. Neurodevelopmental CNVs are associated with intellectual disability, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), conditions typically diagnosed by medical practitioners. However, neurodevelopmental CNVs may have additional, early developmental impacts that have yet to be examined in unselected populations. Methods Carriers of known ND CNVs were identified in two UK birth cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC) (carriers=144, controls=6217) and the Millennium Cohort Study (MCS) (carriers=151, controls=6559). In ALSPAC, we assessed associations between CNV carrier status and: birth complications, preschool development, cognitive ability, neurodevelopmental conditions (ASD, ADHD, reading, language, and motor difficulties), psychiatric, social and educational outcomes. Corresponding phenotypes were identified in MCS and meta-analysed, where available. Results In ALSPAC, neurodevelopmental CNVs were associated with low cognitive ability, ADHD and ASD. Neurodevelopmental CNV carriers showed greater likelihood of preterm birth, fine and gross motor delay, difficulties in motor coordination, language, and reading, and special educational needs (SEND). Meta-analysis with available measures in MCS identified elevated likelihood of ASD, ADHD, low birthweight, reading difficulties, SEND, and peer problems. Discussion Neurodevelopmental CNVs are associated with a broad range of developmental impacts. While clinicians who see children with intellectual disability, ASD, or ADHD may be aware of the impacts of CNVs and consider genetic testing, our investigation suggests that this training and awareness may need to extend to other professional groups (e.g. speech and language therapists).

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine Research Institutes & Centres > MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Elsevier
ISSN:	0006-3223
Date of First Compliant Deposit:	18 March 2025
Date of Acceptance:	5 March 2025
Last Modified:	19 Mar 2025 12:30
URI:	https://orca.cardiff.ac.uk/id/eprint/176955

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