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

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive l...

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Vydáno v:	Nature genetics Ročník 49; číslo 1; s. 27 - 35
Hlavní autoři:	Merico, Daniele, Antaki, Danny, Shetty, Aniket, Gujral, Madhusudan, Brandler, William M, Malhotra, Dheeraj, Alexander, Madeline, Belliveau, Richard A, Bergen, Sarah E, Bertalan, Marcelo, Bevilacqua, Elizabeth, Cantor, Rita M, Carrera, Noa, Cormican, Paul, Crespo-Facorro, Benedicto, Curtis, David, Davidson, Michael, Degenhardt, Franziska, Del Favero, Jurgen, DeLisi, Lynn E, Dudbridge, Frank, Eichhammer, Peter, Eriksson, Johan, Essioux, Laurent, Farrell, Martilias S, Freedman, Robert, Freimer, Nelson B, Georgieva, Lyudmila, Gershon, Elliot S, Giegling, Ina, Godard, Stephanie, Goldstein, Jacqueline I, Hamshere, Marian L, Hartmann, Annette M, Hofman, Andrea, Kähler, Anna K, Kalaydjieva, Luba, Kelly, Brian J, Lee, S Hong, Legge, Sophie E, Lerer, Bernard, Levy, Deborah L, Maher, Brion S, Mattingsdal, Morten, McDonald, Colm, Metspalu, Andres, Milanova, Vihra, Morris, Derek W, Murray, Robin M, Nestadt, Gerald, Nicodemus, Kristin K, Nordin, Annelie, Oh, Sang-Yun, Olsen, Line, Van Os, Jim, Pantelis, Christos, Pers, Tune H, Powell, John, Price, Alkes, Pulver, Ann E, Purcell, Shaun M, Rasmussen, Henrik B, Richards, Alexander L, Roussos, Panos, Schall, Ulrich, Schwab, Sibylle G, Smoller, Jordan W, Spencer, Chris C A, Stahl, Eli A, Stroup, T Scott, Suvisaari, Jaana, Svrakic, Dragan M, Szatkiewicz, Jin P, Veijola, Juha, Waddington, John, Webb, Bradley T, Williams, Nigel M, Williams, Stephanie, Wolen, Aaron R, Adolfsson, Rolf, Blackwood, Douglas H R, Bramon, Elvira, Buxbaum, Joseph D, Collier, David A, Daly, Mark J, Darvasi, Ariel, Domenici, Enrico, Gill, Michael, Iwata, Nakao, Jablensky, Assen V, Jönsson, Erik G, Kirov, George, Knight, Jo, Levinson, Douglas F, Ophoff, Roel A, Owen, Michael J, Rietschel, Marcella, Rujescu, Dan, O'Donovan, Michael C, Neale, Benjamin M
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.01.2017 Nature Publishing Group
Témata:	45 45/23 631/208/212 692/308/2056 692/699/476/1799 Agriculture Analysis Animal Genetics and Genomics Biomedical and Life Sciences Biomedicine Cancer Research Case-Control Studies Consortia Copy number variations Data processing Datasets Development and progression DNA Copy Number Variations DNA Copy Number Variations - genetics Female Gene Function Genetic aspects Genetic Loci Genetic Loci - genetics Genetic Markers Genetic Markers - genetics Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Genomics Genotype Human Genetics Human health and pathology Humans Life Sciences Male Mental disorders Meta-analysis Pipelines Quality control Risk Factors Schizophrenia Schizophrenia - genetics Studies Working groups
ISSN:	1061-4036, 1546-1718, 1546-1718
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Shrnutí:	The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia. 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.
Bibliografie:	SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-2 content type line 23 PMCID: PMC5737772 these authors co-supervised the study these authors contributed equally
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.3725