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Cognitive performance and functional outcomes of carriers of pathogenic copy number variants: analysis of the UK Biobank

  • Kimberley M. Kendall (a1), Matthew Bracher-Smith (a2), Harry Fitzpatrick (a3), Amy Lynham (a4), Elliott Rees (a4), Valentina Escott-Price (a5), Michael J. Owen (a6), Michael C. O'Donovan (a7), James T.R. Walters (a8) and George Kirov (a8)...

Abstract

Background

Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.

Aims

We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.

Method

We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.

Results

Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.

Conclusions

CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.

Declaration of interest

None.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Correspondence: Professor George Kirov, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK. Email: kirov@cardiff.ac.uk

Footnotes

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These authors contributed equally to this work.

Footnotes

References

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Cognitive performance and functional outcomes of carriers of pathogenic copy number variants: analysis of the UK Biobank

  • Kimberley M. Kendall (a1), Matthew Bracher-Smith (a2), Harry Fitzpatrick (a3), Amy Lynham (a4), Elliott Rees (a4), Valentina Escott-Price (a5), Michael J. Owen (a6), Michael C. O'Donovan (a7), James T.R. Walters (a8) and George Kirov (a8)...
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