Polygenic scores stratify neurodevelopmental copy number variant carrier cognitive outcomes in the UK Biobank

Dinneen, Thomas J., Ní Ghrálaigh, Fiana, Ormond, Cathal, Heron, Elizabeth A., Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Lopez, Lorna M. and Gallagher, Louise 2024. Polygenic scores stratify neurodevelopmental copy number variant carrier cognitive outcomes in the UK Biobank. npj Genomic Medicine 9 (1) , 43. 10.1038/s41525-024-00426-8

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Abstract

Rare copy-number variants associated with neurodevelopmental conditions (ND-CNVs) exhibit variable expressivity of clinical, physical, behavioural outcomes. Findings from clinically ascertained cohorts suggest this variability may be partly due to additional genetic variation. Here, we assessed the impact of polygenic scores (PGS) and rare variants on ND-CNV carrier fluid intelligence (FI) scores in the UK Biobank. Greater PGS for cognition (PSCog) and educational attainment (PSEA) is associated with increased FI scores in all ND-CNVs (n = 1317), 15q11.2 del. (n = 543), and 16p13.11 dup. carriers (n = 275). No association of rare variants associated with intellectual disability, autism, or putatively loss-of-function, brain-expressed genes was found. Positive predictive values in the first deciles of PScog and PSEA showed a two- to five-fold increase in the rate of low FI scores compared to baseline rates. These findings demonstrate that PGS can stratify ND-CNV carrier cognitive outcomes in a population-based cohort.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	30 September 2024
Date of Acceptance:	4 September 2024
Last Modified:	30 Sep 2024 10:30
URI:	https://orca.cardiff.ac.uk/id/eprint/172471

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