@article{3219140,
    title = "Mapping genomic loci implicates genes and synaptic biology in schizophrenia",
    author = "Trubetskoy, V. and Pardiñas, A.F. and Qi, T. and Panagiotaropoulou, G. and Awasthi, S. and Bigdeli, T.B. and Bryois, J. and Chen, C.-Y. and Dennison, C.A. and Hall, L.S. and Lam, M. and Watanabe, K. and Frei, O. and Ge, T. and Harwood, J.C. and Koopmans, F. and Magnusson, S. and Richards, A.L. and Sidorenko, J. and Wu, Y. and Zeng, J. and Grove, J. and Kim, M. and Li, Z. and Voloudakis, G. and Zhang, W. and Adams, M. and Agartz, I. and Atkinson, E.G. and Agerbo, E. and Al Eissa, M. and Albus, M. and Alexander, M. and Alizadeh, B.Z. and Alptekin, K. and Als, T.D. and Amin, F. and Arolt, V. and Arrojo, M. and Athanasiu, L. and Azevedo, M.H. and Bacanu, S.A. and Bass, N.J. and Begemann, M. and Belliveau, R.A. and Bene, J. and Benyamin, B. and Bergen, S.E. and Blasi, G. and Bobes, J. and Bonassi, S. and Braun, A. and Bressan, R.A. and Bromet, E.J. and Bruggeman, R. and Buckley, P.F. and Buckner, R.L. and Bybjerg-Grauholm, J. and Cahn, W. and Cairns, M.J. and Calkins, M.E. and Carr, V.J. and Castle, D. and Catts, S.V. and Chambert, K.D. and Chan, R.C.K. and Chaumette, B. and Cheng, W. and Cheung, E.F.C. and Chong, S.A. and Cohen, D. and Consoli, A. and Cordeiro, Q. and Costas, J. and Curtis, C. and Davidson, M. and Davis, K.L. and de Haan, L. and Degenhardt, F. and DeLisi, L.E. and Demontis, D. and Dickerson, F. and Dikeos, D. and Dinan, T. and Djurovic, S. and Duan, J. and Ducci, G. and Dudbridge, F. and Eriksson, J.G. and Fañanás, L. and Faraone, S.V. and Fiorentino, A. and Forstner, A. and Frank, J. and Freimer, N.B. and Fromer, M. and Frustaci, A. and Gadelha, A. and Genovese, G. and Gershon, E.S. and Giannitelli, M. and Giegling, I. and Giusti-Rodríguez, P. and Godard, S. and Goldstein, J.I. and González Peñas, J. and González-Pinto, A. and Gopal, S. and Gratten, J. and Green, M.F. and Greenwood, T.A. and Guillin, O. and Gülöksüz, S. and Gur, R.E. and Gur, R.C. and Gutiérrez, B. and Hahn, E. and Hakonarson, H. and Haroutunian, V. and Hartmann, A.M. and Harvey, C. and Hayward, C. and Henskens, F.A. and Herms, S. and Hoffmann, P. and Howrigan, D.P. and Ikeda, M. and Iyegbe, C. and Joa, I. and Julià, A. and Kähler, A.K. and Kam-Thong, T. and Kamatani, Y. and Karachanak-Yankova, S. and Kebir, O. and Keller, M.C. and Kelly, B.J. and Khrunin, A. and Kim, S.-W. and Klovins, J. and Kondratiev, N. and Konte, B. and Kraft, J. and Kubo, M. and Kučinskas, V. and Kučinskiene, Z.A. and Kusumawardhani, A. and Kuzelova-Ptackova, H. and Landi, S. and Lazzeroni, L.C. and Lee, P.H. and Legge, S.E. and Lehrer, D.S. and Lencer, R. and Lerer, B. and Li, M. and Lieberman, J. and Light, G.A. and Limborska, S. and Liu, C.-M. and Lönnqvist, J. and Loughland, C.M. and Lubinski, J. and Luykx, J.J. and Lynham, A. and Macek, M., Jr and Mackinnon, A. and Magnusson, P.K.E. and Maher, B.S. and Maier, W. and Malaspina, D. and Mallet, J. and Marder, S.R. and Marsal, S. and Martin, A.R. and Martorell, L. and Mattheisen, M. and McCarley, R.W. and McDonald, C. and McGrath, J.J. and Medeiros, H. and Meier, S. and Melegh, B. and Melle, I. and Mesholam-Gately, R.I. and Metspalu, A. and Michie, P.T. and Milani, L. and Milanova, V. and Mitjans, M. and Molden, E. and Molina, E. and Molto, M.D. and Mondelli, V. and Moreno, C. and Morley, C.P. and Muntané, G. and Murphy, K.C. and Myin-Germeys, I. and Nenadić, I. and Nestadt, G. and Nikitina-Zake, L. and Noto, C. and Nuechterlein, K.H. and O'Brien, N.L. and O'Neill, F.A. and Oh, S.-Y. and Olincy, A. and Ota, V.K. and Pantelis, C. and Papadimitriou, G.N. and Parellada, M. and Paunio, T. and Pellegrino, R. and Periyasamy, S. and Perkins, D.O. and Pfuhlmann, B. and Pietiläinen, O. and Pimm, J. and Porteous, D. and Powell, J. and Quattrone, D. and Quested, D. and Radant, A.D. and Rampino, A. and Rapaport, M.H. and Rautanen, A. and Reichenberg, A. and Roe, C. and Roffman, J.L. and Roth, J. and Rothermundt, M. and Rutten, B.P.F. and Saker-Delye, S. and Salomaa, V. and Sanjuan, J. and Santoro, M.L. and Savitz, A. and Schall, U. and Scott, R.J. and Seidman, L.J. and Sharp, S.I. and Shi, J. and Siever, L.J. and Sigurdsson, E. and Sim, K. and Skarabis, N. and Slominsky, P. and So, H.-C. and Sobell, J.L. and Söderman, E. and Stain, H.J. and Steen, N.E. and Steixner-Kumar, A.A. and Stögmann, E. and Stone, W.S. and Straub, R.E. and Streit, F. and Strengman, E. and Stroup, T.S. and Subramaniam, M. and Sugar, C.A. and Suvisaari, J. and Svrakic, D.M. and Swerdlow, N.R. and Szatkiewicz, J.P. and Ta, T.M.T. and Takahashi, A. and Terao, C. and Thibaut, F. and Toncheva, D. and Tooney, P.A. and Torretta, S. and Tosato, S. and Tura, G.B. and Turetsky, B.I. and Üçok, A. and Vaaler, A. and van Amelsvoort, T. and van Winkel, R. and Veijola, J. and Waddington, J. and Walter, H. and Waterreus, A. and Webb, B.T. and Weiser, M. and Williams, N.M. and Witt, S.H. and Wormley, B.K. and Wu, J.Q. and Xu, Z. and Yolken, R. and Zai, C.C. and Zhou, W. and Zhu, F. and Zimprich, F. and Atbaşoğlu, E.C. and Ayub, M. and Benner, C. and Bertolino, A. and Black, D.W. and Bray, N.J. and Breen, G. and Buccola, N.G. and Byerley, W.F. and Chen, W.J. and Cloninger, C.R. and Crespo-Facorro, B. and Donohoe, G. and Freedman, R. and Galletly, C. and Gandal, M.J. and Gennarelli, M. and Hougaard, D.M. and Hwu, H.-G. and Jablensky, A.V. and McCarroll, S.A. and Moran, J.L. and Mors, O. and Mortensen, P.B. and Müller-Myhsok, B. and Neil, A.L. and Nordentoft, M. and Pato, M.T. and Petryshen, T.L. and Pirinen, M. and Pulver, A.E. and Schulze, T.G. and Silverman, J.M. and Smoller, J.W. and Stahl, E.A. and Tsuang, D.W. and Vilella, E. and Wang, S.-H. and Xu, S. and Adolfsson, R. and Arango, C. and Baune, B.T. and Belangero, S.I. and Børglum, A.D. and Braff, D. and Bramon, E. and Buxbaum, J.D. and Campion, D. and Cervilla, J.A. and Cichon, S. and Collier, D.A. and Corvin, A. and Curtis, D. and Forti, M.D. and Domenici, E. and Ehrenreich, H. and Escott-Price, V. and Esko, T. and Fanous, A.H. and Gareeva, A. and Gawlik, M. and Gejman, P.V. and Gill, M. and Glatt, S.J. and Golimbet, V. and Hong, K.S. and Hultman, C.M. and Hyman, S.E. and Iwata, N. and Jönsson, E.G. and Kahn, R.S. and Kennedy, J.L. and Khusnutdinova, E. and Kirov, G. and Knowles, J.A. and Krebs, M.-O. and Laurent-Levinson, C. and Lee, J. and Lencz, T. and Levinson, D.F. and Li, Q.S. and Liu, J. and Malhotra, A.K. and Malhotra, D. and McIntosh, A. and McQuillin, A. and Menezes, P.R. and Morgan, V.A. and Morris, D.W. and Mowry, B.J. and Murray, R.M. and Nimgaonkar, V. and Nöthen, M.M. and Ophoff, R.A. and Paciga, S.A. and Palotie, A. and Pato, C.N. and Qin, S. and Rietschel, M. and Riley, B.P. and Rivera, M. and Rujescu, D. and Saka, M.C. and Sanders, A.R. and Schwab, S.G. and Serretti, A. and Sham, P.C. and Shi, Y. and St Clair, D. and Stefánsson, H. and Stefansson, K. and Tsuang, M.T. and van Os, J. and Vawter, M.P. and Weinberger, D.R. and Werge, T. and Wildenauer, D.B. and Yu, X. and Yue, W. and Holmans, P.A. and Pocklington, A.J. and Roussos, P. and Vassos, E. and Verhage, M. and Visscher, P.M. and Yang, J. and Posthuma, D. and Andreassen, O.A. and Kendler, K.S. and Owen, M.J. and Wray, N.R. and Daly, M.J. and Huang, H. and Neale, B.M. and Sullivan, P.F. and Ripke, S. and Walters, J.T.R. and O'Donovan, M.C. and Indonesia Schizophrenia Consortium and PsychENCODE and Psychosis Endophenotypes International Consortium and SynGO Consortium and Schizophrenia Working Group of the Psychiatric Genomics Consortium",
    journal = "Nature Metabolism",
    year = "2022",
    volume = "604",
    number = "7906",
    pages = "502-508",
    publisher = "NLM (Medline)",
    doi = "10.1038/s41586-022-04434-5",
    keywords = "allele;  genetic predisposition;  genetics;  genome-wide association study;  genomics;  human;  schizophrenia;  single nucleotide polymorphism, Alleles;  Genetic Predisposition to Disease;  Genome-Wide Association Study;  Genomics;  Humans;  Polymorphism, Single Nucleotide;  Schizophrenia",
    abstract = "Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies. © 2022. The Author(s), under exclusive licence to Springer Nature Limited."
}