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Journal article

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

By Marshall, Christian R.; Howrigan, Daniel P.; Merico, Daniele; Thiruvahindrapuram, Bhooma; Wu, Wenting; Greer, Douglas S.; Antaki, Danny; Shetty, Aniket; Holmans, Peter A.; Pinto, Dalila; Gujral, Madhusudan; Brandler, William M.; Malhotra, Dheeraj; Wang, Zhouzhi; Fuentes Fajarado, Karin V.; Maile, Michelle S.; Ripke, Stephan; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amin, Farooq; Atkins, Joshua; Bacanu, Silviu A.; Belliveau, Richard A.; Bergen, Sarah E.; Bertalan, Marcelo; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Bulik-Sullivan, Brendan; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Cairns, Murray J.; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberley D.; Cheng, Wei; Cloninger, C. Robert; Cohen, David; Cormican, Paul; Craddock, Nick; Crespo-Facorro, Benedicto; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; DeLisi, Lynn E.; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farh, Kai How; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedman, Joseph I.; Forstner, Andreas J.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Gratten, Jacob; De Haan, Lieuwe; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas1; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Huang, Hailiang; Ikeda, Masashi; Joa, Inge; Kähler, Anna K.; Kahn, René S.; Kalaydjieva, Luba; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kelly, Brian J.; Kennedy, James L.; Kim, Yunjung; Knowles, James A.; Konte, Bettina; Laurent, Claudine; Lee, Phil; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Levy, Deborah L.; Liang, Kung Yee; Lieberman, Jeffrey; Lönnqvist, Jouko; Loughland, Carmel M.; Magnusson, Patrik K E; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Mattheisen, Manuel2; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Müller-Myhsok, Bertram; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nisenbaum, Laura; Nordin, Annelie; O'Callaghan, Eadbhard; O'Dushlaine, Colm; Oh, Sang Yun; Olincy, Ann; Olsen, Line; O'Neill, F. Anthony; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Perkins, Diana O.; Pers, Tune Hannes3,4,5; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Powell, John; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, H. B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Savitz, Adam; Schall, Ulrich; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Silverman, Jeremy M.; Smoller, Jordan W.; Söderman, Erik; Spencer, Chris C A; Stahl, Eli A.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Thirumalai, Srinivas; Tooney, Paul A.; Veijola, Juha; Visscher, Peter M.; Waddington, John; Walsh, Dermot; Webb, Bradley T.; Weiser, Mark; Wildenauer, Dieter B.; Williams, Nigel M.; Williams, Stephanie; Witt, Stephanie H.; Wolen, Aaron R.; Wormley, Brandon K.; Wray, Naomi R.; Wu, J. Q.; Zai, Clement C.; Adolfsson, Rolf; Andreassen, Ole A.; Blackwood, Douglas H R; Bramon, Elvira; Buxbaum, Joseph D.; Cichon, Sven; Collier, David A.; Corvin, Aiden; Daly, Mark J.; Darvasi, Ariel; Domenici, Enrico; Esko, Tõnu; Gejman, Pablo V.; Gill, Michael; Gurling, Hugh; Hultman, Christina M.; Iwata, Nakao; Jablensky, Assen V.; Jönsson, Erik G.; Kendler, Kenneth S.; Kirov, George; Knight, Jo; Levinson, Douglas F.; Li, Qingqin S.; McCarroll, Steven A.; McQuillin, Andrew; Moran, Jennifer L.; Mowry, Bryan J.; Nöthen, Markus M.; Ophoff, Roel A.; Owen, Michael J.; Palotie, Aarno; Pato, Carlos N.; Petryshen, Tracey L.; Posthuma, Danielle; Rietschel, Marcella; Riley, Brien P.; Rujescu, Dan; Sklar, Pamela; St Clair, David; Walters, James T R; Werge, Thomas6; Sullivan, Patrick F.; O'Donovan, Michael C.; Scherer, Stephen W.; Neale, Benjamin M.; Sebat, Jonathan ...and 253 more

From

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
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
Keywords

Genetics

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