title: Does rare matter? Copy number variants at 16p11.2 and the risk of psychosis: a systematic review of literature and meta-analysis.
abstract: 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.
authors.affiliation: Division of Psychiatry, University College London, United Kingdom; North East London Foundation NHS Trust, London, United Kingdom; Cognition, Schizophrenia & Imaging Laboratory, Department of Psychosis Studies, The Institute of Psychiatry, King's College London, United Kingdom.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Giaroli
authors.affiliation: Division of Psychiatry, University College London, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bass
authors.affiliation: Division of Psychiatry, University College London, United Kingdom.
authors.forename: Andre
authors.initials: A
authors.lastname: Strydom
authors.affiliation: Division of Psychiatry, University College London, United Kingdom.
authors.forename: Khadijia
authors.initials: K
authors.lastname: Rantell
authors.affiliation: Division of Psychiatry, University College London, United Kingdom. Electronic address: a.mcquillin@ucl.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
mesh_terms: D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D011618:Psychotic Disorders / Q000235:genetics*
keywords: 16p11.2; Bipolar disorders; CNV; Copy number variation; Duplication; Psychosis; Schizoaffective disorder; Schizophrenia