TY - JOUR
T1 - Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
AU - Psychosis Endophenotypes International Consortium
AU - CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium
AU - Marshall, Christian R.
AU - Howrigan, Daniel P.
AU - Merico, Daniele
AU - Thiruvahindrapuram, Bhooma
AU - Wu, Wenting
AU - Greer, Douglas S.
AU - Antaki, Danny
AU - Shetty, Aniket
AU - Holmans, Peter A.
AU - Pinto, Dalila
AU - Gujral, Madhusudan
AU - Brandler, William M.
AU - Malhotra, Dheeraj
AU - Wang, Zhouzhi
AU - Fuentes Fajarado, Karin V.
AU - Maile, Michelle S.
AU - Ripke, Stephan
AU - Agartz, Ingrid
AU - Albus, Margot
AU - Alexander, Madeline
AU - Amin, Farooq
AU - Atkins, Joshua
AU - Bacanu, Silviu A.
AU - Belliveau, Richard A.
AU - Bergen, Sarah E.
AU - Bertalan, Marcelo
AU - Bevilacqua, Elizabeth
AU - Bigdeli, Tim B.
AU - Black, Donald W.
AU - Bruggeman, Richard
AU - Buccola, Nancy G.
AU - Buckner, Randy L.
AU - Bulik-Sullivan, Brendan
AU - Byerley, William
AU - Cahn, Wiepke
AU - Cai, Guiqing
AU - Cairns, Murray J.
AU - Campion, Dominique
AU - Cantor, Rita M.
AU - Carr, Vaughan J.
AU - Carrera, Noa
AU - Catts, Stanley V.
AU - Chambert, Kimberley D.
AU - Cheng, Wei
AU - Cloninger, C. Robert
AU - Cohen, David
AU - Cormican, Paul
AU - Craddock, Nick
AU - Crespo-Facorro, Benedicto
AU - Meier, Sandra
N1 - Funding Information:
Core funding for the Psychiatric Genomics Consortium is from the US National Institute of Mental Health (NIMH, U01 MH094421).
Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
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U2 - 10.1038/ng.3725
DO - 10.1038/ng.3725
M3 - Article
C2 - 27869829
AN - SCOPUS:84997770295
SN - 1061-4036
VL - 49
SP - 27
EP - 35
JO - Nature Genetics
JF - Nature Genetics
IS - 1
ER -