Cited by 443Genomic variations and chromosomal abnormalitiesSchizophrenia research and treatmentGenetic Associations and Epidemiology

Analysis of copy number variations at 15 schizophrenia-associated loci

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Rees, Elliott, Walters, James T. R., Georgieva, Lyudmila, Isles, Anthony R., Chambert, Kimberly D., Richards, Alexander L., Mahoney-Davies, Gerwyn, Legge, Sophie E. +5 more·2014·British Journal of Psychiatry

Abstract

Background: A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain. Aims: To determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia (n= 6882) and controls (n= 6316), and (b) combining our results with those from previous studies. Method: We used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets. Results: We found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1,NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia (P<4.1×10−4). Conclusions: We strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations.

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  • Rees et al. found a significant association between the 15q11.2 BP1-BP2 microdeletion and schizophrenia, with a frequency of 0.64 (44/6882) among individuals having schizophrenia and the microdeletion in their study.

    “Rees et al. [40] found a significant association between the microdeletion and schizophrenia with the frequency of individuals having schizophrenia and the microdeletion from their study was 0.64 (44/6882).”

    From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [40]

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  1. [20]Kirov G Grozeva D Norton N Ivanov D Mantripragada KK Holmans P Support for the involvement of large CNVS in the pathogenesis of schizophrenia. Hum Mol Genet 2009; 18: 1497– 503 19181681 PMC2664144
  2. [35]Botto LD May K Fernhoff PM Correa A Coleman K Rasmussen SA A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 2003; 112: 101– 7 12837874

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Authors
Rees, E., Walters, J. T. R., Georgieva, L., Isles, A. R., Chambert, K. D., Richards, A. L., Mahoney-Davies, G., Legge, S. E., Moran, J. L., McCarroll, S. A., O'Donovan, M. C., Owen, M. J., & Kirov, G.
Affiliations
  • Broad Institute (US)
  • Cardiff University (GB)
Corresponding author
Kirov, George
Venue
British Journal of Psychiatry
Published
2014-02
Volume
204
Issue
2
Pages
108-114
ISSN
  • 0007-1250 (ISSN-L)
  • 1472-1465
OpenAlex
W2086619421
Cited by
443
References
55
Citations by year
2026: 15 · 2025: 24 · 2024: 29 · 2023: 26 · 2022: 25 · 2021: 39 · 2020: 53 · 2019: 50 · 2018: 38 · 2017: 27 · 2016: 42 · 2015: 42 · 2014: 30 · 2013: 2
FWCI
25.66
Type
journal article
Language
en
Open access
Locations
  • The British Journal of Psychiatry (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • University of Pennsylvania
  • Johns Hopkins University (HHSN268200782096C, P01 CA089392)
  • Wellcome Trust (G0801418)
  • Broad Institute
  • Leverhulme Trust
  • British Medical Association
  • European Commission (241909)
  • Cardiff University (G0800509)
  • National Institutes of Health (HHSN268200782096C, CA089392)
  • Directorate for Biological Sciences
  • Stanley Center for Psychiatric Research, Broad Institute
  • Medical Research Council (G0801418, MR/L010305/1, G0800509, HHSN268200782096C)
  • Biotechnology and Biological Sciences Research Council
  • National Institute on Drug Abuse (P50DA019706)
  • National Human Genome Research Institute (U01HG004446, HHSN268200782096C)
  • National Eye Institute (R01EY020483)
  • National Cancer Institute (P50CA097007, R01CA133996, P01CA089392, P50CA084724, P50CA093459)
  • National Institute of Environmental Health Sciences (R01ES011740)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
copy number variation, schizophrenia, genetic susceptibility, 1q21.1 deletion, NRXN1, 15q11.2, 22q11.2, 16p11.2 duplication, genetic comorbidity
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Chromosome Deletion, Female, Humans, Male, Middle Aged, Prader-Willi Syndrome, Schizophrenia, Case-Control Studies, Angelman Syndrome, Genomic Imprinting, Genetic Predisposition to Disease, Young Adult, Genetic Loci, DNA Copy Number Variations, Genotyping Techniques

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