Association of copy number variation across the genome with neuropsychiatric traits in the general population

Anna L. Guyatt, Evie Stergiakouli, Joanna Martin, James Walters, Michael O'Donovan, Michael Owen, Anita Thapar, George Kirov, Santiago Rodriguez, Dheeraj Rai, Stan Zammit, Tom R. Gaunt*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

25 Citations (Scopus)
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Copy number variants (CNVs) are associated with psychiatric conditions in clinical populations. The relationship between rare CNV burden and neuropsychiatric traits in young, general populations is underexplored. A total of 6,807 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were studied. CNVs were inferred from single nucleotide polymorphism-array data using PennCNV. After excluding children with known candidate CNVs for schizophrenia (SCZ), rare (<1%) CNV burden (total number of genes affected by CNVs, total length of CNVs, and largest CNV carried) was analyzed in relation to: psychotic experiences (PEs) and anxiety/depression in adolescence; autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), ASD and ADHD traits, and cognitive measures during childhood. Outcomes were also assessed in relation to known SCZ CNVs. The number of genes affected by rare CNVs was associated with a continuous measure of ASD: the standardized mean difference [SMD] per gene affected was increased by 0.018 [95%CI 0.011,0.025], p = 3e-07 for duplications and by 0.021 [95%CI 0.010, 0.032], p = 1e-04 for deletions. In line with our published results on educational attainment in ALSPAC, intelligence quotient (IQ) was associated with CNV burden: the SMD per gene affected was −0.017 [95%CI −0.025, −0.008] p = 1e-04 for duplications and −0.023 [95%CI −0.037, −0.009], p =.002 for deletions. Associations were also observed for measures of coherence, attention, memory, and social cognition. SCZ-associated deletions were associated with IQ (SMD: −0.617 [95%CI −0.936, −0.298], p = 2e-04), but not with PEs or other traits. We found that rare CNV burden and known SCZ candidate CNVs are associated with neuropsychiatric phenotypes in a nonclinically ascertained sample of young people.

Original languageEnglish
Pages (from-to)489-502
Number of pages14
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number5
Early online date24 Apr 2018
Publication statusPublished - Jul 2018


  • childhood
  • genetic epidemiology
  • structural variation


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  • NIHR BRC Mental Health

    Gunnell, D. J.


    Project: Research, Parent

  • IEU Theme 2

    Flach, P. A., Gaunt, T. R. & Gaunt, T. R.


    Project: Research

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