Abstract
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.
Highlights
Concerning rarer variation, in a large study of the burden of rare Copy number variants (CNVs) and cognitive phenotypes in unselected populations, including Avon Longitudinal Study of Parents and Children (ALSPAC), we previously found that these variants were negatively associated with educational attainment (Männik et al, 2015)
FI G URE 3 Number of genes affected by rare CNVs in relation to neuropsychiatric traits. This analysis is a regression of the number of genes affected by rare CNVs in relation to neuropsychiatric traits
3.2.2 | Total length of rare CNVs. The associations for this analysis are generally similar to that of the “number of genes” analysis, above, which may be explained by the fact that the total length of rare CNV regions and the number of genes affected by rare CNVs are correlated at r [Spearman] 5 .76 (r [Pearson] 5 .64)
Summary
Depressive disorder (MDD) may be less heritable (0.37, [95%CI 0.31, 0.42]) (Sullivan, Neale, & Kendler, 2000), there is variance in. There is substantial pleiotropy between many of these psychiatric phenotypes: in a study of five disorders (SCZ, BPD, MDD, ASD, ADHD), consistent genetic correlations (rG) estimated from single nucleotide polymorphism (SNP) data by both restricted maximum likelihood) and linkage disequilibrium-score regression were found, including the highest rG of 0.79 for SCZ and BPD (Bulik-Sullivan et al, 2015). This same study observed more modest (yet still substantial) rG values of 0.14 and 0.23 for SCZ/ASD and SCZ/ADHD. The secondary objective was to test the relationship of known SCZ candidate CNVs with the traits studied
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