Copy Number Variations and Neuropsychiatric Diseases


Copy number variants (CNVs) are submicroscopic deletions and duplications of deoxyribonucleic acid (DNA) segments, which can have a high impact on gene expression. Methods to explore CNVs include array comparative genomic hybridisation, single‚Äźnucleotide polymorphism microarrays and whole genome sequencing. Rare CNVs are strongly associated with neuropsychiatric diseases including autism spectrum disorder, schizophrenia, bipolar disorder and disruptions to some specific loci have been related to more than one disorder. The chromosome 22q11.21 deletion is so far the locus identified with the highest risk, 82% for any psychiatric disorder. De novo copy number events, those present in cases but not in their parents, also have a significant risk for any of these disorders, with an overall risk of 13% to develop a neuropsychiatric disorder if present anywhere in the genome.

Key Concepts:

  • Copy number variants are so far the most potent sources of genetic risk for neuropsychiatric disease.

  • Rare and de novo events are associated with neuropsychiatric disorders.

Keywords: copy number variants; CNV; mental disorders; bipolar disorder; schizophrenia; autism

Figure 1.

Feasibility of identifying genetic variants by risk allele frequency and strength of genetic effect. This classic figure has become somewhat outdated by recent discoveries in common disease. First, rare CNV variants with high effect have been found as reviewed here. Furthermore, de novo CNVs are a common event in neuropsychiatric common disease with high effect, and de novo SNPs, reported so far only in SZ, have a similar effect (Xu et al., ). Reproduced from Manolio et al. () with permission from Nature Publishing Group. © Nature Publishing Group.



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Noor A, Lionel AC, Cohen‐Woods S et al. (2014) Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 165(4): 303–313. PMID:24700553.

Psychiatric Genomics Consortium (2014).

International Society of Psychiatric Genetics (2014) Genetic Testing Statement.

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Alliey‐Rodriguez, Ney, and Gershon, Elliot S(Jul 2014) Copy Number Variations and Neuropsychiatric Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0022451]