Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Psychosis Endophenotypes International Consortium, Christian R Marshall, Daniel P Howrigan, Daniele Merico, Bhooma Thiruvahindrapuram, Wenting Wu, Douglas S Greer, Danny Antaki, Aniket Shetty, Peter A Holmans, Dalila Pinto, Madhusudan Gujral, William M Brandler, Dheeraj Malhotra, Zhouzhi Wang, Karin V Fuentes Fajarado, Michelle S Maile, Stephan Ripke, Ingrid Agartz, Margot AlbusMadeline Alexander, Farooq Amin, Joshua Atkins, Silviu-Alin Bacanu, Richard A. Belliveau, Sarah E. Bergen, Marcelo Bertalan, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W Black, Richard Bruggeman, Nancy G Buccola, Randy L Buckner, Brendan K Bulik-Sullivan, William F Byerley, Wiepke Cahn, Guiqing Cai, Murray J Cairns, Dominique Campion, Rita M Cantor, Vaughan J Carr, Noa Carrera, Stanley V Catts, Kimberley D. Chambert, Wei-Tzu Cheng, C Robert Cloninger, David J Cohen, Paul Cormican, Andrew McIntosh, Kristin Nicodemus, Douglas H R Blackwood

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalNature Genetics
Issue number1
Early online date21 Nov 2016
Publication statusPublished - 11 Jul 2017

Keywords / Materials (for Non-textual outputs)

  • Case-Control Studies
  • DNA Copy Number Variations
  • Female
  • Genetic Loci
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Risk Factors
  • Schizophrenia
  • Comparative Study
  • Journal Article


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