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

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 Albus, Madeline AlexanderFarooq Amin, Joshua Atkins, Silviu A. Bacanu, Richard A. Belliveau, Sarah E. Bergen, Marcelo Ertalan, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, Brendan Bulik-Sullivan, William 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 Cheng, C. Robert Cloninger, David Cohen, Paul Cormican, Inez Myin-Germeys, Jim Van Os, CNV, Schizophrenia Working Group, Psychosis Endophenotypes

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 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
Publication statusPublished - Jan 2017


  • GENE
  • 16P11.2
  • RISK
  • CNVS


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