1. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
- Author
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Marshall, C.R. (Christian), Howrigan, D.P. (Daniel P.), Merico, D. (Daniele), Thiruvahindrapuram, B. (Bhooma), Wu, W. (Wenting), Greer, D.S. (Douglas S.), Antaki, D. (Danny), Shetty, A. (Aniket), Holmans, P.A. (Peter A.), Pinto, D. (Duane), Gujral, M. (Madhusudan), Brandler, W.M. (William M.), Malhotra, D. (Dheeraj), Wang, Z. (Zhouzhi), Fuentes Fajarado, K.V. (Karin V.), Maile, M.S. (Michelle S.), Ripke, S. (Stephan), Agartz, I. (Ingrid), Albus, M. (Margot), Alexander, M. (Madeline), Amin, F. (Farooq), Atkins, J. (Joshua), Bacanu, S.A. (Silviu), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Bertalan, M. (Marcelo), Bevilacqua, E. (Elizabeth), Bigdeli, T.B. (Tim B.), Black, D.W. (Donald), Bruggeman, R. (Richard), Buccola, N.G. (Nancy G), Buckner, M., Bulik-Sullivan, B.K. (Brendan), Byerley, W.F. (William F), Cahn, W. (Wiepke), Cai, G. (Guiqing), Cairns, M.J. (Murray J.), Campion, D. (Dominique), Cantor, R.M., Carr, V.J. (Vaughan), Carrera, N. (Noa), Catts, S.V. (Stanley), Chambert, K. (Kimberly), Cheng, W. (Wei), Cloninger, C.R. (C Robert), Cohen, D.J. (David J.), Cormican, P. (Paul), Craddock, N.J. (Nick), Crespo-Facorro, B. (Benedicto), Crowley, J.J. (James), Curtis, D. (David), Davidson, M.W. (Michael ), Davis, K.L. (Kenneth), Degenhardt, F., Del-Favero, J. (Jurgen), Delisi, L.E. (Lynn), Dikeos, D. (Dimitris), Dinan, T. (Timothy), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drapeau, E. (Elodie), Duan, J. (Jubao), Dudbridge, F. (Frank), Eichhammer, P. (Peter), Hagen, K. (Knut), Escott-Price, V. (Valentina), Essioux, L. (Laurent), Fanous, A.H. (Ayman H.), Farh, K.-H. (Kai-How), Farrell, M.S. (Martilias), Frank, J. (Josef), Franke, L. (Lude), Freedman, R. (Robert), Freimer, N.B. (Nelson), Friedman, J.I. (Joseph), Forstner, A.J. (Andreas), Fromer, M. (Menachem), Genovese, G. (Giulio), Georgieva, I. (Irina), Gershon, E.S. (Elliot S.), Giegling, I. (Ina), Giusti-Rodríguez, P. (Paola), Godard, S. (Stephanie), Goldstein, J.I. (Jacqueline), Gratten, J. (Jacob), Haan, L. (Lieuwe) de, Hamshere, M.L. (Marian), Hansen, M. (Mark), Hansen, T. (Thomas), Haroutunian, V. (Vahram), Hartmann, A.M. (Annette M), Henskens, F.A. (Frans), Herms, S. (Stefan), Hirschhorn, J.N. (Joel), Hoffmann, P. (Per), Hofman, A. (Andrea), Huang, H. (Hailiang), Ikeda, M. (Masashi), Joa, I. (Inge), Kähler, J. (Jan), Kahn, R. (René), Kalaydjieva, L. (Luba), Karjalainen, J. (Juha), Kavanagh, D. (David), Keller, M.C. (Matthew C), Kelly, B.J. (Brian J.), Kennedy, J.L., Kim, Y. (Yunjung), Knowles, J.A. (James A), Konte, B. (Bettina), Laurent, C. (Camille), Lee, P.H. (Phil), Lee, S.U. (Seung), Legge, S.E. (Sophie), Lerer, B. (Bernard), Levy, D.L. (Deborah L.), Liang, K.-Y. (Kung-Yee), Lieberman, A.P. (Andrew), Lönnqvist, J. (Jouko), Loughland, C.M. (Carmel), Magnusson, P.K. (Patrik), Maher, B.S. (Brion), Maier, W. (Wolfgang), Mallet, V. (Vincent), Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), McCarley, R.W. (Robert), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Meier, S., Meijer, C. (Carin), Melle, I. (Ingrid), Mesholam-Gately, R.I. (Raquelle), Metspalu, A. (Andres), Michie, P.T. (Patricia), Milani, L. (Lili), Milanova, V. (Vihra), Mokrab, Y. (Younes), Morris, D.W. (Derek W), Müller-Myhsok, B. (B.), Murphy, K.C. (Kieran), Murray, R. (Robin), Myin-Germeys, I. (Inez), Nenadic, I. (Igor), Nertney, D.A. (Deborah), Nestadt, G. (Gerald), Nicodemus, K.K. (Kristin), Nisenbaum, L. (Laura), Nordin, A. (Annelie), O'Callaghan, E. (Eadbhard), O'Dushlaine, C. (Colm), Oh, S.-Y. (Sang-Yun), Olincy, A. (Ann), Olsen, L. (Line), O'Neill, F.A. (Francis), Os, J. (Jim) van, Pantelis, C. (Christos), Papadimitriou, G.N. (George), Parkhomenko, E. (Elena), Pato, C. (Carlos), Paunio, T. (Tiina), Perkins, D.O. (Diana O.), Pers, T.H. (Tune), Pietiläinen, O.P.H. (Olli), Pimm, J. (Jonathan), Pocklington, A.J. (Andrew), Powell, J. (John), Price, A. (Alkes), Pulver, A.E. (Ann), Purcell, S.M. (Shaun M.), Quested, D.J. (Digby J), Rasmussen, H.B. (Henrik B), Reichenberg, A. (Abraham), Reimers, B. (Bernhard), Richards, A. (Alex), Roffman, J.L. (Joshua), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Savitz, A. (Adam), Schall, J.D. (Jeffrey), Schulze, T.G. (Thomas), Schwab, S.G. (Sibylle G.), Scolnick, E. (Edward), Scott, R.J. (Rodney), Seidman, L.J. (Larry), Shi, J. (Jianxin), Silverman, J.M. (Jeremy M.), Smoller, J.W., Söderman, E. (Erik), Spencer, C.C.A. (Chris C.), Stahl, E.A. (Eli A.), Strengman, E. (Eric), Strohmaier, J., Stroup, T.S. (T. Scott), Suvisaari, J. (Jaana), Svrakic, D.M. (Dragan), Szatkiewicz, J.P. (Jin P.), Thirumalai, S. (Srinivasa), Tooney, P.A. (Paul A.), Veijola, J. (Juha), Visscher, P.M. (Peter), Waddington, J. (Joanne), Walsh, D. (Dermot), Webb, B.T. (Bradley T.), Weiser, M. (Mark), Wildenauer, D.B. (Dieter), Williams, N.M. (Nigel M.), Williams, S. (Stephanie), Witt, S.H. (Stephanie H), Wolen, A.R. (Aaron), Wormley, B.K. (Brandon K.), Wray, N.R. (Naomi), Wu, J.Q. (Jing Qin), Zai, C.C. (Clement), Adolfsson, R., Andreassen, O.A. (Ole A.), Blackwood, D.H.R. (Douglas), Bramon, E. (Elvira), Buxbaum, J.D. (Joseph D), Cichon, S. (Sven), Collier, D.A. (David), Corvin, A. (Aiden), Daly, M.J. (Mark J.), Darvasi, A. (Ariel), Domenici, E. (Enrico), Esko, T. (Tõnu), Gejman, P.V. (Pablo), Gill, M. (Michael), Gurling, H. (Hugh), Hultman, C.M. (Christina), Iwata, N. (Nakao), Jablensky, A. (Assen), Jönsson, E.G. (Erik), Kendler, K. (K.), Kirov, G. (George), Knight, J. (Jo), Levinson, D.F. (Douglas F.), Li, Q.S. (Qingqin S.), McCarroll, S.A. (Steve), McQuillin, A. (Andrew), Moran, J.L. (Jennifer L), Mowry, B.J. (Bryan J), Nöthen, M.M. (Markus), Ophoff, R.A. (Roel A.), Owen, M.J. (Michael), Palotie, A. (Aarno), Petryshen, T.L. (Tracey), Posthuma, D. (Danielle), Rietschel, M. (Marcella), Riley, B.P. (Brien P.), Rujescu, D. (Dan), Sklar, P. (Pamela), St Clair, D. (David), Walters, J.T. (James), Werge, T.M. (Thomas), Sullivan, P.F. (Patrick), O'donovan, M.C. (Michael), Scherer, S.W. (Stephen), Neale, B.M. (Benjamin), Sebat, J. (Jonathan), Marshall, C.R. (Christian), Howrigan, D.P. (Daniel P.), Merico, D. (Daniele), Thiruvahindrapuram, B. (Bhooma), Wu, W. (Wenting), Greer, D.S. (Douglas S.), Antaki, D. (Danny), Shetty, A. (Aniket), Holmans, P.A. (Peter A.), Pinto, D. (Duane), Gujral, M. (Madhusudan), Brandler, W.M. (William M.), Malhotra, D. (Dheeraj), Wang, Z. (Zhouzhi), Fuentes Fajarado, K.V. (Karin V.), Maile, M.S. (Michelle S.), Ripke, S. (Stephan), Agartz, I. (Ingrid), Albus, M. (Margot), Alexander, M. (Madeline), Amin, F. (Farooq), Atkins, J. (Joshua), Bacanu, S.A. (Silviu), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Bertalan, M. (Marcelo), Bevilacqua, E. (Elizabeth), Bigdeli, T.B. (Tim B.), Black, D.W. (Donald), Bruggeman, R. (Richard), Buccola, N.G. (Nancy G), Buckner, M., Bulik-Sullivan, B.K. (Brendan), Byerley, W.F. (William F), Cahn, W. (Wiepke), Cai, G. (Guiqing), Cairns, M.J. (Murray J.), Campion, D. (Dominique), Cantor, R.M., Carr, V.J. (Vaughan), Carrera, N. (Noa), Catts, S.V. (Stanley), Chambert, K. (Kimberly), Cheng, W. (Wei), Cloninger, C.R. (C Robert), Cohen, D.J. (David J.), Cormican, P. (Paul), Craddock, N.J. (Nick), Crespo-Facorro, B. (Benedicto), Crowley, J.J. (James), Curtis, D. (David), Davidson, M.W. (Michael ), Davis, K.L. (Kenneth), Degenhardt, F., Del-Favero, J. (Jurgen), Delisi, L.E. (Lynn), Dikeos, D. (Dimitris), Dinan, T. (Timothy), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drapeau, E. (Elodie), Duan, J. (Jubao), Dudbridge, F. (Frank), Eichhammer, P. (Peter), Hagen, K. (Knut), Escott-Price, V. (Valentina), Essioux, L. (Laurent), Fanous, A.H. (Ayman H.), Farh, K.-H. (Kai-How), Farrell, M.S. (Martilias), Frank, J. (Josef), Franke, L. (Lude), Freedman, R. (Robert), Freimer, N.B. (Nelson), Friedman, J.I. (Joseph), Forstner, A.J. (Andreas), Fromer, M. (Menachem), Genovese, G. (Giulio), Georgieva, I. (Irina), Gershon, E.S. (Elliot S.), Giegling, I. (Ina), Giusti-Rodríguez, P. (Paola), Godard, S. (Stephanie), Goldstein, J.I. (Jacqueline), Gratten, J. (Jacob), Haan, L. (Lieuwe) de, Hamshere, M.L. (Marian), Hansen, M. (Mark), Hansen, T. (Thomas), Haroutunian, V. (Vahram), Hartmann, A.M. (Annette M), Henskens, F.A. (Frans), Herms, S. (Stefan), Hirschhorn, J.N. (Joel), Hoffmann, P. (Per), Hofman, A. (Andrea), Huang, H. (Hailiang), Ikeda, M. (Masashi), Joa, I. (Inge), Kähler, J. (Jan), Kahn, R. (René), Kalaydjieva, L. (Luba), Karjalainen, J. (Juha), Kavanagh, D. (David), Keller, M.C. (Matthew C), Kelly, B.J. (Brian J.), Kennedy, J.L., Kim, Y. (Yunjung), Knowles, J.A. (James A), Konte, B. (Bettina), Laurent, C. (Camille), Lee, P.H. (Phil), Lee, S.U. (Seung), Legge, S.E. (Sophie), Lerer, B. (Bernard), Levy, D.L. (Deborah L.), Liang, K.-Y. (Kung-Yee), Lieberman, A.P. (Andrew), Lönnqvist, J. (Jouko), Loughland, C.M. (Carmel), Magnusson, P.K. (Patrik), Maher, B.S. (Brion), Maier, W. (Wolfgang), Mallet, V. (Vincent), Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), McCarley, R.W. (Robert), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Meier, S., Meijer, C. (Carin), Melle, I. (Ingrid), Mesholam-Gately, R.I. (Raquelle), Metspalu, A. (Andres), Michie, P.T. (Patricia), Milani, L. (Lili), Milanova, V. (Vihra), Mokrab, Y. (Younes), Morris, D.W. (Derek W), Müller-Myhsok, B. (B.), Murphy, K.C. (Kieran), Murray, R. (Robin), Myin-Germeys, I. (Inez), Nenadic, I. (Igor), Nertney, D.A. (Deborah), Nestadt, G. (Gerald), Nicodemus, K.K. (Kristin), Nisenbaum, L. (Laura), Nordin, A. (Annelie), O'Callaghan, E. (Eadbhard), O'Dushlaine, C. (Colm), Oh, S.-Y. (Sang-Yun), Olincy, A. (Ann), Olsen, L. (Line), O'Neill, F.A. (Francis), Os, J. (Jim) van, Pantelis, C. (Christos), Papadimitriou, G.N. (George), Parkhomenko, E. (Elena), Pato, C. (Carlos), Paunio, T. (Tiina), Perkins, D.O. (Diana O.), Pers, T.H. (Tune), Pietiläinen, O.P.H. (Olli), Pimm, J. (Jonathan), Pocklington, A.J. (Andrew), Powell, J. (John), Price, A. (Alkes), Pulver, A.E. (Ann), Purcell, S.M. (Shaun M.), Quested, D.J. (Digby J), Rasmussen, H.B. (Henrik B), Reichenberg, A. (Abraham), Reimers, B. (Bernhard), Richards, A. (Alex), Roffman, J.L. (Joshua), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Savitz, A. (Adam), Schall, J.D. (Jeffrey), Schulze, T.G. (Thomas), Schwab, S.G. (Sibylle G.), Scolnick, E. (Edward), Scott, R.J. (Rodney), Seidman, L.J. (Larry), Shi, J. (Jianxin), Silverman, J.M. (Jeremy M.), Smoller, J.W., Söderman, E. (Erik), Spencer, C.C.A. (Chris C.), Stahl, E.A. (Eli A.), Strengman, E. (Eric), Strohmaier, J., Stroup, T.S. (T. Scott), Suvisaari, J. (Jaana), Svrakic, D.M. (Dragan), Szatkiewicz, J.P. (Jin P.), Thirumalai, S. (Srinivasa), Tooney, P.A. (Paul A.), Veijola, J. (Juha), Visscher, P.M. (Peter), Waddington, J. (Joanne), Walsh, D. (Dermot), Webb, B.T. (Bradley T.), Weiser, M. (Mark), Wildenauer, D.B. (Dieter), Williams, N.M. (Nigel M.), Williams, S. (Stephanie), Witt, S.H. (Stephanie H), Wolen, A.R. (Aaron), Wormley, B.K. (Brandon K.), Wray, N.R. (Naomi), Wu, J.Q. (Jing Qin), Zai, C.C. (Clement), Adolfsson, R., Andreassen, O.A. (Ole A.), Blackwood, D.H.R. (Douglas), Bramon, E. (Elvira), Buxbaum, J.D. (Joseph D), Cichon, S. (Sven), Collier, D.A. (David), Corvin, A. (Aiden), Daly, M.J. (Mark J.), Darvasi, A. (Ariel), Domenici, E. (Enrico), Esko, T. (Tõnu), Gejman, P.V. (Pablo), Gill, M. (Michael), Gurling, H. (Hugh), Hultman, C.M. (Christina), Iwata, N. (Nakao), Jablensky, A. (Assen), Jönsson, E.G. (Erik), Kendler, K. (K.), Kirov, G. (George), Knight, J. (Jo), Levinson, D.F. (Douglas F.), Li, Q.S. (Qingqin S.), McCarroll, S.A. (Steve), McQuillin, A. (Andrew), Moran, J.L. (Jennifer L), Mowry, B.J. (Bryan J), Nöthen, M.M. (Markus), Ophoff, R.A. (Roel A.), Owen, M.J. (Michael), Palotie, A. (Aarno), Petryshen, T.L. (Tracey), Posthuma, D. (Danielle), Rietschel, M. (Marcella), Riley, B.P. (Brien P.), Rujescu, D. (Dan), Sklar, P. (Pamela), St Clair, D. (David), Walters, J.T. (James), Werge, T.M. (Thomas), Sullivan, P.F. (Patrick), O'donovan, M.C. (Michael), Scherer, S.W. (Stephen), Neale, B.M. (Benjamin), and Sebat, J. (Jonathan)
- 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.
- Published
- 2017
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