Does rare matter? Copy number variants at 16p11.2 and the risk of psychosis: a systematic review of literature and meta-analysis

Schizophr Res. 2014 Nov;159(2-3):340-6. doi: 10.1016/j.schres.2014.09.025. Epub 2014 Oct 11.


Background: In the last 5 years an increasing number of studies have found that individuals who have micro-duplications at 16p11.2 may have an increased risk of mental disorders including psychotic syndromes.

Objective: Our main aim was to review all the evidence in the literature for the association between copy number variants (CNVs) at 16p11.2 and psychosis.

Methods: We have conducted a systematic review and a meta-analysis utilising the PRISMA statement criteria. We included all original studies (published in English) which presented data on CNVs at 16p11.2 in patients affected by schizophrenia, schizoaffective disorder or bipolar disorder.

Results: We retrieved 15 articles which fulfilled our inclusion criteria. Eleven articles were subsequently selected for a meta-analysis that showed a 10 fold increased risk of psychosis in patients with proximal 16p11.2 duplications. We conducted a second meta-analysis of those studies with low risk of overlap in order to obtain the largest possible sample with the lowest risk of repeated results: 5 studies were selected and we found an odds ratio (OR) of 14.4 (CI=5.2-39.8; p<0.001) for psychosis with proximal 16p11.2 duplications. The results were not significant for micro-deletions in the same region. Finally extracting only those studies that included patients with schizophrenia we found an OR=16.0 (CI=5.4-47.3: p<0.001) CONCLUSIONS: There is a fourteen fold-increased risk of psychosis and a sixteen fold increased risk of schizophrenia in individuals with micro-duplication at proximal 16p11.2.

Keywords: 16p11.2; Bipolar disorders; CNV; Copy number variation; Duplication; Psychosis; Schizoaffective disorder; Schizophrenia.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Chromosomes, Human, Pair 16 / genetics*
  • DNA Copy Number Variations / genetics*
  • Genetic Predisposition to Disease*
  • Humans
  • Psychotic Disorders / genetics*