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Title: Biological insights from 108 schizophrenia-associated genetic loci
Contributor(s): Ripke, Stephan (author); Neale, Benjamin M (author); Pers, Tune H (author); Julia, Antonio (author); Kahn, Rene S (author); Kalaydjieva, Luba (author); Karachanak-Yankova, Sena (author); Karjalainen, Juha (author); Kavanagh, David (author); Keller, Matthew C (author); Kennedy, James L (author); Khrunin, Andrey (author); Kim, Yunjung (author); Agartz, Ingrid (author); Klovins, Janis (author); Knowles, James A (author); Konte, Bettina (author); Kucinskas, Vaidutis (author); Ausrele Kucinskiene, Zita (author); Kuzelova-Ptackova, Hana (author); Kahler, Anna K (author); Laurent, Claudine (author); Lee Chee Keong, Jimmy (author); Lee, Sang Hong  (author); Agerbo, Esben (author); Legge, Sophie E (author); Lerer, Bernard (author); Li, Miaoxin (author); Li, Tao (author); Liang, Kung-Yee (author); Lieberman, Jeffrey (author); Limborska, Svetlana (author); Loughland, Carmel M (author); Lubinski, Jan (author); Lonnqvist, Jouko (author); Albus, Margot (author); Macek Jr, Milan (author); Magnusson, Patrik K E (author); Maher, Brion S (author); Maier, Wolfgang (author); Mallet, Jacques (author); Marsal, Sara (author); Mattheisen, Manuel (author); Mattingsdal, Morten (author); McCarley, Robert W (author); McDonald, Colm (author); Alexander, Madeline (author); McIntosh, Andrew M (author); Meier, Sandra (author); Meijer, Carin J (author); Melegh, Bela (author); Melle, Ingrid (author); Mesholam-Gately, Raquelle I (author); Metspalu, Andres (author); Michie, Patricia T (author); Milani, Lili (author); Milanova, Vihra (author); Amin, Farooq (author); Mokrab, Younes (author); Morris, Derek W (author); Mors, Ole (author); Murphy, Kieran C (author); Murray, Robin M (author); Myin-Germeys, Inez (author); Muller-Myhsok, Bertram (author); Nelis, Mari (author); Nenadic, Igor (author); Nertney, Deborah A (author); Bacanu, Silviu A (author); Nestadt, Gerald (author); Nicodemus, Kristin K (author); Nikitina-Zake, Liene (author); Nisenbaum, Laura (author); Nordin, Annelie (author); O'Callaghan, Eadbhard (author); O'Dushlaine, Colm (author); O'Neill, F Anthony (author); Oh, Sang-Yun (author); Olincy, Ann (author); Begemann, Martin (author); Olsen, Line (author); Van Os, Jim (author); Psychosis Endophenotypes International Consortium, (author); Pantelis, Christos (author); Papadimitriou, George N (author); Papiol, Sergi (author); Parkhomenko, Elena (author); Pato, Michele T (author); Paunio, Tiina (author); Pejovic-Milovancevic, Milica (author); Belliveau Jr, Richard A (author); Perkins, Diana O (author); Pietilainen, Olli (author); Pimm, Jonathan (author); Pocklington, Andrew J (author); Powell, John (author); Price, Alkes (author); Pulver, Ann E (author); Purcell, Shaun M (author); Quested, Digby (author); Rasmussen, Henrik B (author); Bene, Judit (author); Reichenberg, Abraham (author); Reimers, Mark A (author); Richards, Alexander L (author); Roffman, Joshua L (author); Roussos, Panos (author); Ruderfer, Douglas M (author); Salomaa, Veikko (author); Sanders, Alan R (author); Schall, Ulrich (author); Schubert, Christian R (author); Corvin, Aiden (author); Bergen, Sarah E (author); Schulze, Thomas G (author); Schwab, Sibylle G (author); Scolnick, Edward M (author); Scott, Rodney J (author); Seidman, Larry J (author); Shi, Jianxin (author); Sigurdsson, Engilbert (author); Silagadze, Teimuraz (author); Silverman, Jeremy M (author); Sim, Kang (author); Bevilacqua, Elizabeth (author); Slominsky, Petr (author); Smoller, Jordan W (author); So, Hon-Cheong (author); Spencer, Chris C A (author); Stahl, Eli A (author); Stefansson, Hreinn (author); Steinberg, Stacy (author); Stogmann, Elisabeth (author); Straub, Richard E (author); Strengman, Eric (author); Bigdeli, Tim B (author); Strohmaier, Jana (author); Stroup, T Scott (author); Subramaniam, Mythily (author); Suvisaari, Jaana (author); Svrakic, Dragan M (author); Szatkiewicz, Jin P (author); Soderman, Erik (author); Thirumalai, Srinivas (author); Toncheva, Draga (author); Tosato, Sarah (author); Black, Donald W (author); Veijola, Juha (author); Waddington, John (author); Walsh, Dermot (author); Wang, Dai (author); Wang, Qiang (author); Webb, Bradley T (author); Weiser, Mark (author); Wildenauer, Dieter B (author); Williams, Nigel M (author); Williams, Stephanie (author); Bruggeman, Richard (author); Witt, Stephanie H (author); Wolen, Aaron R (author); Wong, Emily H M (author); Wormley, Brandon K (author); Xi, Hualin Simon (author); Zai, Clement C (author); Zheng, Xuebin (author); Zimprich, Fritz (author); Wray, Naomi R (author); Stefansson, Kari (author); Buccola, Nancy G (author); Visscher, Peter M (author); Wellcome Trust Case-Control Consortium, (author); Adolfsson, Rolf (author); Andreassen, Ole A (author); Blackwood, Douglas H R (author); Bramon, Elvira (author); Buxbaum, Joseph D (author); Borglum, Anders D (author); Cichon, Sven (author); Darvasi, Ariel (author); Buckner, Randy L (author); Domenici, Enrico (author); Ehrenreich, Hannelore (author); Esko, Tonu (author); Gejman, Pablo V (author); Gill, Michael (author); Gurling, Hugh (author); Hultman, Christina M (author); Iwata, Nakao (author); Jablensky, Assen V (author); Jonsson, Erik G (author); Byerley, William (author); Kendler, Kenneth S (author); Kirov, George (author); Knight, Jo (author); Lencz, Todd (author); Levinson, Douglas F (author); Li, Qingqin S (author); Liu, Jianjun (author); Malhotra, Anil K (author); McCarroll, Steven A (author); McQuillin, Andrew (author); Cahn, Wiepke (author); Moran, Jennifer L (author); Mortensen, Preben B (author); Mowry, Bryan J (author); Nothen, Markus M (author); Ophoff, Roel A (author); Owen, Michael J (author); Palotie, Aarno (author); Pato, Carlos N (author); Petryshen, Tracey L (author); Posthuma, Danielle (author); Cai, Guiqing (author); Rietschel, Marcella (author); Riley, Brien P (author); Rujescu, Dan (author); Sham, Pak C (author); Sklar, Pamela (author); St Clair, David (author); Weinberger, Daniel R (author); Wendland, Jens R (author); Werge, Thomas (author); Daly, Mark J (author); Walters, James T R (author); Campion, Dominique (author); Sullivan, Patrick F (author); O'Donovan, Michael C (author); Cantor, Rita M (author); Carr, Vaughan J (author); Carrera, Noa (author); Catts, Stanley V (author); Chambert, Kimberly D (author); Chan, Raymond C K (author); Chen, Ronald Y L (author); Chen, Eric Y H (author); Cheng, Wei (author); Farh, Kai-How (author); Cheung, Eric F C (author); Chong, Siow Ann (author); Cloninger, C Robert (author); Cohen, David (author); Cohen, Nadine (author); Cormican, Paul (author); Craddock, Nick (author); Crowley, James J (author); Curtis, David (author); Davidson, Michael (author); Holmans, Peter A (author); Davis, Kenneth L (author); Degenhardt, Franziska (author); Del Favero, Jurgen (author); Demontis, Ditte (author); Dikeos, Dimitris (author); Dinan, Timothy (author); Djurovic, Srdjan (author); Donohoe, Gary (author); Drapeau, Elodie (author); Duan, Jubao (author); Lee, Phil (author); Dudbridge, Frank (author); Durmishi, Naser (author); Eichhammer, Peter (author); Eriksson, Johan (author); Escott-Price, Valentina (author); Essioux, Laurent (author); Fanous, Ayman H (author); Farrell, Martilias S (author); Frank, Josef (author); Franke, Lude (author); Bulik-Sullivan, Brendan (author); Freedman, Robert (author); Freimer, Nelson B (author); Friedl, Marion (author); Friedman, Joseph I (author); Fromer, Menachem (author); Genovese, Giulio (author); Georgieva, Lyudmila (author); Giegling, Ina (author); Giusti-Rodriguez, Paola (author); Godard, Stephanie (author); Collier, David A (author); Goldstein, Jacqueline I (author); Golimbet, Vera (author); Gopal, Srihari (author); Gratten, Jacob (author); de Haan, Lieuwe (author); Hammer, Christian (author); Hamshere, Marian L (author); Hansen, Mark (author); Hansen, Thomas (author); Haroutunian, Vahram (author); Huang, Hailiang (author); Hartmann, Annette M (author); Henskens, Frans A (author); Herms, Stefan (author); Hirschhorn, Joel N (author); Hoffmann, Per (author); Hofman, Andrea (author); Hollegaard, Mads V (author); Hougaard, David M (author); Ikeda, Masashi (author); Joa, Inge (author)
Publication Date: 2014
Open Access: Yes
DOI: 10.1038/nature13595Open Access Link
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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.
Publication Type: Journal Article
Source of Publication: Nature, 511(7510), p. 421-427
Publisher: Nature Publishing Group
Place of Publication: London, United Kingdom
ISSN: 1476-4687
Field of Research (FOR): 060412 Quantitative Genetics (incl. Disease and Trait Mapping Genetics)
110319 Psychiatry (incl. Psychotherapy)
060408 Genomics
Socio-Economic Objective (SEO): 970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
920110 Inherited Diseases (incl. Gene Therapy)
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
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