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Biological insights from 108 schizophrenia-associated genetic loci
Ripke, S. (Corresponding Author) ; Neale, B. M. ; Corvin, A. ; Walters, J. T. R. ; Farh, K.-H. ; Holmans, P. A. ; Lee, P. ; Bulik-Sullivan, B. ; Collier, D. A. ; Huang, H. ; Pers, T. H. ; Agartz, I. ; Agerbo, E. ; Albus, M. ; Alexander, M. ; Amin, F. ; Bacanu, S. A. ; Begemann, M. ; Belliveau Jr, R. A. ; Bene, J. ; Bergen, S. E. ; Bevilacqua, E. ; Bigdeli, T. B. ; Black, D. W. ; Bruggeman, R. ; Buccola, N. G. ; Buckner, R. L. ; Byerley, W. ; Cahn, W. ; Cai, G. ; Campion, D. ; Cantor, R. M. ; Carr, V. J. ; Carrera, N. ; Catts, S. V. ; Chambert, K. D. ; Chan, R. C. K. ; Chen, R. Y. L. ; Chen, E. Y. H. ; Cheng, W. ; Cheung, E. F. C. ; Ann Chong, S. ; Robert Cloninger, C. ; Cohen, D. ; Cohen, N. ; Cormican, P. ; Craddock, N. ; Crowley, J. J. ; Curtis, D. ; Davidson, M. ; Davis, K. L. ; Degenhardt, F. ; Del Favero, J. ; Demontis, D. ; Dikeos, D. ; Dinan, T. ; Djurovic, S. ; Donohoe, G. ; Drapeau, E. ; Duan, J. ; Dudbridge, F. ; Durmishi, N. ; Eichhammer, P. ; Eriksson, J. ; Escott-Price, V. ; Essioux, L. ; Fanous, A. H. ; Farrell, M. S. ; Frank, J. ; Franke, L. ; Freedman, R. ; Freimer, N. B. ; Friedl, M. ; Friedman, J. I. ; Fromer, M. ; Genovese, G. ; Georgieva, L. ; Giegling, I. ; Giusti-Rodríguez, P. ; Godard, S. ; Goldstein, J. I. ; Golimbet, V. ; Gopal, S. ; Gratten, J. ; de Haan, L. ; Hammer, C. ; Hamshere, M. L. ; Hansen, M. ; Hansen, T. ; Haroutunian, V. ; Hartmann, A. M. ; Henskens, F. A. ; Herms, S. ; Hirschhorn, J. N. ; Hoffmann, P.FZJ* ; Hofman, A. ; Hollegaard, M. V. ; Hougaard, D. M. ; Ikeda, M. ; Joa, I. ; Julià, A. ; Kahn, R. S. ; Kalaydjieva, L. ; Karachanak-Yankova, S. ; Karjalainen, J. ; Kavanagh, D. ; Keller, M. C. ; Kennedy, J. L. ; Khrunin, A. ; Kim, Y. ; Klovins, J. ; Knowles, J. A. ; Konte, B. ; Kucinskas, V. ; Ausrele Kucinskiene, Z. ; Kuzelova-Ptackova, H. ; Kähler, A. K. ; Laurent, C. ; Lee Chee Keong, J. ; Hong Lee, S. ; Legge, S. E. ; Lerer, B. ; Li, M. ; Li, T. ; Liang, K.-Y. ; Lieberman, J. ; Limborska, S. ; Loughland, C. M. ; Lubinski, J. ; Lönnqvist, J. ; Macek Jr, M. ; Magnusson, P. K. E. ; Maher, B. S. ; Maier, W. ; Mallet, J. ; Marsal, S. ; Mattheisen, M. ; Mattingsdal, M. ; McCarley, R. W. ; McDonald, C. ; McIntosh, A. M. ; Meier, S. ; Meijer, C. J. ; Melegh, B. ; Melle, I. ; Mesholam-Gately, R. I. ; Metspalu, A. ; Michie, P. T. ; Milani, L. ; Milanova, V. ; Mokrab, Y. ; Morris, D. W. ; Mors, O. ; Murphy, K. C. ; Murray, R. M. ; Myin-Germeys, I. ; Müller-Myhsok, B. ; Nelis, M. ; Nenadic, I. ; Nertney, D. A. ; Nestadt, G. ; Nicodemus, K. K. ; Nikitina-Zake, L. ; Nisenbaum, L. ; Nordin, A. ; O’Callaghan, E. ; O’Dushlaine, C. ; O’Neill, F. A. ; Oh, S.-Y. ; Olincy, A. ; Olsen, L. ; Van Os, J. ; Endophenotypes International Consortium, P. ; Pantelis, C. ; Papadimitriou, G. N. ; Papiol, S. ; Parkhomenko, E. ; Pato, M. T. ; Paunio, T. ; Pejovic-Milovancevic, M. ; Perkins, D. O. ; Pietiläinen, O. ; Pimm, J. ; Pocklington, A. J. ; Powell, J. ; Price, A. ; Pulver, A. E. ; Purcell, S. M. ; Quested, D. ; Rasmussen, H. B. ; Reichenberg, A. ; Reimers, M. A. ; Richards, A. L. ; Roffman, J. L. ; Roussos, P. ; Ruderfer, D. M. ; Salomaa, V. ; Sanders, A. R. ; Schall, U. ; Schubert, C. R. ; Schulze, T. G. ; Schwab, S. G. ; Scolnick, E. M. ; Scott, R. J. ; Seidman, L. J. ; Shi, J. ; Sigurdsson, E. ; Silagadze, T. ; Silverman, J. M. ; Sim, K. ; Slominsky, P. ; Smoller, J. W. ; So, H.-C. ; Spencer, C. A. ; Stahl, E. A. ; Stefansson, H. ; Steinberg, S. ; Stogmann, E. ; Straub, R. E. ; Strengman, E. ; Strohmaier, J. ; Scott Stroup, T. ; Subramaniam, M. ; Suvisaari, J. ; Svrakic, D. M. ; Szatkiewicz, J. P. ; Söderman, E. ; Thirumalai, S. ; Toncheva, D. ; Tosato, S. ; Veijola, J. ; Waddington, J. ; Walsh, D. ; Wang, D. ; Wang, Q. ; Webb, B. T. ; Weiser, M. ; Wildenauer, D. B. ; Williams, N. M. ; Williams, S. ; Witt, S. H. ; Wolen, A. R. ; Wong, E. H. M. ; Wormley, B. K. ; Simon Xi, H. ; Zai, C. C. ; Zheng, X. ; Zimprich, F. ; Wray, N. R. ; Stefansson, K. ; Visscher, P. M. ; Trust Case-Control Consortium, W. ; Adolfsson, R. ; Andreassen, O. A. ; Blackwood, D. H. R. ; Bramon, E. ; Buxbaum, J. D. ; Børglum, A. D. ; Cichon, S.FZJ* ; Darvasi, A. ; Domenici, E. ; Ehrenreich, H. ; Esko, T. ; Gejman, P. V. ; Gill, M. ; Gurling, H. ; Hultman, C. M. ; Iwata, N. ; Jablensky, A. V. ; Jönsson, E. G. ; Kendler, K. S. ; Kirov, G. ; Knight, J. ; Lencz, T. ; Levinson, D. F. ; Li, Q. S. ; Liu, J. ; Malhotra, A. K. ; McCarroll, S. A. ; McQuillin, A. ; Moran, J. L. ; Mortensen, P. B. ; Mowry, B. J. ; Nöthen, M. M. ; Ophoff, R. A. ; Owen, M. J. ; Palotie, A. ; Pato, C. N. ; Petryshen, T. L. ; Posthuma, D. ; Rietschel, M. ; Riley, B. P. ; Rujescu, D. ; Sham, P. C. ; Sklar, P. ; St Clair, D. ; Weinberger, D. R. ; Wendland, J. R. ; Werge, T. ; Daly, M. J. ; Sullivan, P. F. ; O’Donovan, M. C.
2014
Nature Publising Group
London [u.a.]
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Please use a persistent id in citations: doi:10.1038/nature13595
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
Contributing Institute(s):
- Strukturelle und funktionelle Organisation des Gehirns (INM-1)
Research Program(s):
- 333 - Pathophysiological Mechanisms of Neurological and Psychiatric Diseases (POF2-333) (POF2-333)
- 89571 - Connectivity and Activity (POF2-89571) (POF2-89571)
Appears in the scientific report
2014
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