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Br J Psychiatry. 2019 May;214(5):297-304. doi: 10.1192/bjp.2018.301. Epub 2019 Feb 15.

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

Author information

1
Wellcome Trust Clinical Research Fellow, MRC Centre for Neuropsychiatric Genetics and Genomics,Cardiff University,UK.
2
PhD Student, MRC Centre for Neuropsychiatric Genetics and Genomics,Cardiff University,UK.
3
Medical Student, School of Medicine,Cardiff University,UK.
4
Research Associate, MRC Centre for Neuropsychiatric Genetics and Genomics,Cardiff University,UK.
5
Professor, Dementia Research Institute,Cardiff University,UK.
6
Director, MRC Centre for Neuropsychiatric Genetics and Genomics,Cardiff University;Director/Clinical Professor, Division of Psychological Medicine and Clinical Neuroscience,Cardiff University; andEmeritus Director, Neuroscience and Mental Health Research Institute,Cardiff University,UK.
7
Deputy Director, Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics,Cardiff University,UK.
8
Professor, Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics,Cardiff University,UK.

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.AimsWe 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 interestNone.

KEYWORDS:

CNV; Townsend Deprivation Index; UK Biobank; cognitive; schizophrenia

PMID:
30767844
PMCID:
PMC6520248
[Available on 2019-11-01]
DOI:
10.1192/bjp.2018.301

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