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

Am J Med Genet B Neuropsychiatr Genet. 2018 Jul;177(5):489-502. doi: 10.1002/ajmg.b.32637. Epub 2018 Apr 24.


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.

Keywords: ALSPAC; childhood; genetic epidemiology; structural variation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anxiety / genetics
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Autism Spectrum Disorder / genetics
  • Child
  • DNA Copy Number Variations / genetics*
  • Depression / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Humans
  • Intelligence / genetics
  • Longitudinal Studies
  • Male
  • Mental Disorders / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Schizophrenia / genetics