Journal article
Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
Mental Health Services Copenhagen1
Aarhus University2
Department of Systems Biology, Technical University of Denmark3
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark4
Behavioral Phenomics, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark5
University of Copenhagen6
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.
Language: | English |
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Publisher: | Nature Publishing Group US |
Year: | 2017 |
Pages: | 27-35 |
ISSN: | 10614036 and 15461718 |
Types: | Journal article |
DOI: | 10.1038/ng.3725 |
ORCIDs: | 0000-0002-8769-0846 , 0000-0003-3622-835X , 0000-0003-3096-4807 , 0000-0002-9520-6209 , 0000-0003-4867-9465 , 0000-0002-5159-8802 , 0000-0003-3586-6587 , 0000-0001-6703-7762 , 0000-0003-1461-5762 , 0000-0002-3307-5741 , 0000-0001-5287-308X , 0000-0002-8442-493X , 0000-0002-0198-4588 , 0000-0002-5323-3102 and 0000-0002-9087-526X |
16P11.2 AUTISM CNVS Case-Control Studies DISORDERS DNA Copy Number Variations DUPLICATIONS Female GENE Genetic Loci Genetic Markers Genetic Predisposition to Disease Genome-Wide Association Study Genotype Humans MUTATIONSGenetics & Heredity Male PHENOTYPES REARRANGEMENTS RISK Risk Factors Schizophrenia