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

    Research output: Contribution to journalJournal articleResearchpeer-review

    204 Downloads (Pure)

    Abstract

    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.
    Original languageEnglish
    JournalNature Genetics
    Volume49
    Issue number1
    Pages (from-to)27-35
    Number of pages9
    ISSN1061-4036
    DOIs
    Publication statusPublished - 2017

    Keywords

    • Genetics

    Fingerprint

    Dive into the research topics of 'Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects'. Together they form a unique fingerprint.

    Cite this