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dc.contributor.authorRipke S, Neale BM, Corvin A, Walters JT, Farh KH, Holmans PA, Lee P, Bulik-Sullivan B, Collier DA, Huang H, Pers TH, Agartz I, Agerbo E, Albus M, Alexander M, Amin F, Bacanu SA, Begemann M, Belliveau RA Jr, Bene J, Bergen SE, Bevilacqua E, Bigdeli TB, Black DW, Bruggeman R, Buccola NG, Buckner RL, Byerley W, Cahn W, Cai G, Campion D, Cantor RM, Carr VJ, Carrera N, Catts SV, Chambert KD, Chan RC, Chen RY, Chen EY, Cheng W, Cheung EF, Chong SA, Cloninger CR, Cohen D, Cohen N, Cormican P, Craddock N, Crowley JJ, Curtis D, Davidson M, Davis KL, 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 AH, Farrell MS, Frank J, Franke L, Freedman R, Freimer NB, Friedl M, Friedman JI, Fromer M, Genovese G, Georgieva L, Giegling I, Giusti-Rodríguez P, Godard S, Goldstein JI, Golimbet V, Gopal S, Gratten J, de Haan L, Hammer C, Hamshere ML, Hansen M, Hansen T, Haroutunian V, Hartmann AM, Henskens FA, Herms S, Hirschhorn JN, Hoffmann P, Hofman A, Hollegaard MV, Hougaard DM, Ikeda M, Joa I, Julià A, Kahn RS, Kalaydjieva L, Karachanak-Yankova S, Karjalainen J, Kavanagh D, Keller MC, Kennedy JL, Khrunin A, Kim Y, Klovins J, Knowles JA, Konte B, Kucinskas V, Ausrele Kucinskiene Z, Kuzelova-Ptackova H, Kähler AK, Laurent C, Keong JL, Lee SH, Legge SE, Lerer B, Li M, Li T, Liang KY, Lieberman J, Limborska S, Loughland CM, Lubinski J, Lönnqvist J, Macek M Jr, Magnusson PK, Maher BS, Maier W, Mallet J, Marsal S, Mattheisen M, Mattingsdal M, McCarley RW, McDonald C, McIntosh AM, Meier S, Meijer CJ, Melegh B, Melle I, Mesholam-Gately RI, Metspalu A, Michie PT, Milani L, Milanova V, Mokrab Y, Morris DW, Mors O, Murphy KC, Murray RM, Myin-Germeys I, Müller-Myhsok B, Nelis M, Nenadic I, Nertney DA, Nestadt G, Nicodemus KK, Nikitina-Zake L, Nisenbaum L, Nordin A, O'Callaghan E, O'Dushlaine C, O'Neill FA, Oh SY, Olincy A, Olsen L, Van Os J, Pantelis C, Papadimitriou GN, Papiol S, Parkhomenko E, Pato MT, Paunio T, Pejovic-Milovancevic M, Perkins DO, Pietiläinen O, Pimm J, Pocklington AJ, Powell J, Price A, Pulver AE, Purcell SM, Quested D, Rasmussen HB, Reichenberg A, Reimers MA, Richards AL, Roffman JL, Roussos P, Ruderfer DM, Salomaa V, Sanders AR, Schall U, Schubert CR, Schulze TG, Schwab SG, Scolnick EM, Scott RJ, Seidman LJ, Shi J, Sigurdsson E, Silagadze T, Silverman JM, Sim K, Slominsky P, Smoller JW, So HC, Spencer CA, Stahl EA, Stefansson H, Steinberg S, Stogmann E, Straub RE, Strengman E, Strohmaier J, Stroup TS, Subramaniam M, Suvisaari J, Svrakic DM, Szatkiewicz JP, Söderman E, Thirumalai S, Toncheva D, Tosato S, Veijola J, Waddington J, Walsh D, Wang D, Wang Q, Webb BT, Weiser M, Wildenauer DB, Williams NM, Williams S, Witt SH, Wolen AR, Wong EH, Wormley BK, Xi HS, Zai CC, Zheng X, Zimprich F, Wray NR, Stefansson K, Visscher PM, Adolfsson R, Andreassen OA, Blackwood DH, Bramon E, Buxbaum JD, Børglum AD, Cichon S, Darvasi A, Domenici E, Ehrenreich H, Esko T, Gejman PV, Gill M, Gurling H, Hultman CM, Iwata N, Jablensky AV, Jönsson EG, Kendler KS, Kirov G, Knight J, Lencz T, Levinson DF, Li QS, Liu J, Malhotra AK, McCarroll SA, McQuillin A, Moran JL, Mortensen PB, Mowry BJ, Nöthen MM, Ophoff RA, Owen MJ, Palotie A, Pato CN, Petryshen TL, Posthuma D, Rietschel M, Riley BP, Rujescu D, Sham PC, Sklar P, St Clair D, Weinberger DR, Wendland JR, Werge T, Daly MJ, Sullivan PF, O'Donovan MC.
dc.date.accessioned2014-09-10T13:35:34Z
dc.date.available2014-09-10T13:35:34Z
dc.date.issued2014-07-24
dc.date.submitted2014
dc.identifier.citationNature 2014, 511 (7510):421-7en
dc.identifier.issn1476-4687
dc.identifier.pmid25056061
dc.identifier.doi10.1038/nature13595
dc.identifier.urihttp://hdl.handle.net/2336/326044
dc.descriptionTo access publisher's full text version of this article click on the hyperlink at the bottom of the pageen
dc.description.abstractSchizophrenia 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.
dc.description.sponsorshipUS National Institute of Mental Health/U01 MH094421en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urlhttp://dx.doi.org/10.1038/nature13595en
dc.relation.urlhttp://www.nature.com/nature/journal/v511/n7510/pdf/nature13595.pdfen
dc.rightsArchived with thanks to Natureen
dc.subjectArfgengien
dc.subjectGenen
dc.subjectGeðklofien
dc.subject.meshGenetic Loci/genetics*en
dc.subject.meshSchizophrenia/genetics*en
dc.subject.meshGenome-Wide Association Study*en
dc.subject.meshSchizophrenia/epidemiologyen
dc.subject.meshBipolar Disorder/geneticsen
dc.titleBiological insights from 108 schizophrenia-associated genetic loci.en
dc.typeArticleen
dc.contributor.departmentMassachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA, Broad Inst MIT & Harvard, Stanley Ctr Psychi[ 1 at Res, Cambridge, MA 02142 USA, Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02142 USA, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA, Univ Ireland Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 8, Ireland, Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales, Cardiff Univ, Natl Ctr Mental Hlth, Cardiff CF24 4HQ, S Glam, Wales, Eli Lilly & Co Ltd, Erl Wood Manor, Windlesham GU20 6PH, Surrey, England, Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England, Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark, Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA, Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA, Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, SE-17176 Stockholm, Sweden, Diakonhjemmet Hosp, Dept Psychiat, N-0319 Oslo, Norway, Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, N-0424 Oslo, Norway, Aarhus Univ, CIRRAU, Ctr Integrat Register Based Res, DK-8210 Aarhus, Denmark, Aarhus Univ, Natl Ctr Register Based Res, DK-8210 Aarhus, Denmark, Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark, State Mental Hosp, D-85540 Haar, Germany, Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA, Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30033 USA, Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA, Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA, Max Planck Inst Expt Med, D-37075 Gottingen, Germany, Univ Pecs, Dept Med Genet, H-7624 Pecs, Hungary, Univ Pecs, Szentagothai Res Ctr, H-7624 Pecs, Hungary, Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden, Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA, Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 RB Groningen, Netherlands, Louisiana State Univ, Hlth Sci Ctr, Sch Nursing, New Orleans, LA 70112 USA, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Boston, MA 02129 USA, Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA, Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA, Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, NL-3584 Utrecht, Netherlands, Icahn Sch Med Mt Sinai, Dept Human Genet, New York, NY 10029 USA, Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA, Ctr Hosp Rouvray, F-76301 Rouen, France, INSERM, U1079, Fac Med, F-76301 Rouen, France, Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA, Schizophrenia Res Inst, Sydney, NSW 2010, Australia, Univ New S Wales, Sch Psychiat, Sydney, NSW 2031, Australia, Univ Queensland, Royal Brisbane & Womens Hosp, St Lucia, Qld 4072, Australia, Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China, Univ Hong Kong, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China, Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China, Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27514 USA, Castle Peak Hosp, Hong Kong, Hong Kong, Peoples R China, Inst Mental Hlth, Singapore 539747, Singapore, Washington Univ, Dept Psychiat, St Louis, MO 63110 USA, Assistance Publ Hop Paris, Dept Child & Adolescent Psychiat, Pierre & Marie Curie Fac Med, F-75013 Paris, France, Inst Intelligent Syst & Robot, F-75013 Paris, France, Blue Note Biosci, Princeton, NJ 08540 USA, Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA, Queen Mary Univ London, Dept Psychol Med, London E1 1BB, England, UCL, Mol Psychiat Lab, Div Psychiat, London WC1E 6JJ, England, Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany, Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany, Univ Antwerp VIB, Dept Mol Genet, Appl Mol Genom Unit, B-2610 Antwerp, Belgium, Aarhus Univ, iSEQ, Ctr Integrat Sequencing, DK-8000 Aarhus C, Denmark, Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark, Univ Athens, Sch Med, Dept Psychiat 1, Athens 11528, Greece, Univ Coll Cork, Dept Psychiat, Cork, Ireland, Oslo Univ Hosp, Dept Med Genet, N-0424 Oslo, Norway, Natl Univ Ireland Galway, Cognit Genet & Therapy Grp, Sch Psychol, Galway, Ireland, Natl Univ Ireland Galway, Discipline Biochem, Galway, Ireland, Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA, NorthShore Univ HealthSyst, Dept Psychiat & Biobehav Sci, Evanston, IL 60201 USA, Univ London London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England, Univ Clin Psychiat, Dept Child & Adolescent Psychiat, Skopje 1000, Macedonia, Univ Regensburg, Dept Psychiat, D-93053 Regensburg, Germany, Univ Helsinki, Cent Hosp, Dept Gen Practice, FI-00014 Helsinki, Finland, Folkhalsan Res Ctr, Helsinki, Finland, Biomedicum Helsinki 1, FI-00290 Helsinki, Finland, Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland, F Hoffmann La Roche & Co Ltd, Pharma Res & Early Dev, Translat Technol & Bioinformat, CH-4070 Basel, Switzerland, Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC 20057 USA, Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA, Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23298 USA, Washington VA Med Ctr, Washington, DC 20422 USA, Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Germany, Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands, Univ Colorado Denver, Dept Psychiat, Aurora, CO 80045 USA, Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA, Univ Halle Wittenberg, Dept Psychiat, D-06112 Halle, Germany, Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA, Univ Munich, Dept Psychiat, D-80336 Munich, Germany, Hop La Pitie Salpetriere, Dept Psychiat, INSERM, Inst Myol, F-75013 Paris, France, Hop La Pitie Salpetriere, Dept Human & Mol Genet, INSERM, Inst Myol, F-75013 Paris, France, Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 115522, Russia, Janssen Res & Dev, Neurosci Therapeut Area, Raritan, NJ 08869 USA, Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia, Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands, Illumina, La Jolla, CA 92122 USA, Mental Hlth Serv Copenhagen, Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, DK-4000 Roskilde, Denmark, Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA, JJ Peters VA Med Ctr, Bronx, NY 10468 USA, Univ Newcastle, Prior Res Ctr Hlth Behav, Newcastle, NSW 2308, Australia, Univ Newcastle, Sch Elect Engn & Comp Sci, Newcastle, NSW 2308, Australia, Univ Basel, Dept Biomed, Div Med Genet, CH-4058 Basel, Switzerland, Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA, Statens Serum Inst, Dept Clin Biochem Immunol & Genet, Sect Neonatal Screening & Hormones, DK-2300 Copenhagen, Denmark, Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 4701192, Japan, Stavanger Univ Hosp, Dept Psychiat, Reg Ctr Clin Res Psychosis, N-4011 Stavanger, Norway, Vall dHebron Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain, Univ Western Australia, Ctr Med Res, Perth, WA 6009, Australia, Univ Western Australia, Perkins Inst Med Res, Perth, WA 6009, Australia, Med Univ, Dept Med Genet, Sofia 1431, Bulgaria, Univ Colorado, Dept Psychol, Boulder, CO 80309 USA, Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON M5T 1R8, Canada, Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada, Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada, Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia, Latvian Biomed Res & Study Ctr, LV-1067 Riga, Latvia, Univ So Calif, Dept Psychiat, Los Angeles, CA 90089 USA, Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA, Vilnius State Univ, Fac Med, LT-01513 Vilnius, Lithuania, 2nd Fac Med, Dept Biol & Med Genet, Prague 15006, Czech Republic, Univ Hosp Motol, Prague 15006, Czech Republic, Pierre & Marie Curie Fac Med, Dept Child & Adolescent Psychiat, F-75013 Paris, France, Duke NUS Grad Med Sch, Singapore 169857, Singapore, Hadassah Hebrew Univ, Med Ctr, Dept Psychiat, IL-91120 Jerusalem, Israel, Univ Hong Kong, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China, Sichuan Univ, Mental Hlth Ctr, Chengdu 610041, Sichuan, Peoples R China, Sichuan Univ, West China Hosp, Psychiat Lab, Chengdu 610041, Sichuan, Peoples R China, Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA, Columbia Univ, Dept Psychiat, New York, NY 10032 USA, Univ Newcastle, Prior Ctr Translat Neurosci & Mental Hlth, Newcastle, NSW 2300, Australia, Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, PL-70453 Szczecin, Poland, Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, FI-00271 Helsinki, Finland, Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA, Univ Bonn, Dept Psychiat, D-53127 Bonn, Germany, Hop La Pitie Salpetriere, CNRS, Lab Genet Mol Neurotransmiss & Proc Neurodegenera, F-75013 Paris, France, Univ Bonn, Dept Genom Math, D-53127 Bonn, Germany, Sorlandet Hosp, Res Unit, N-4604 Kristiansand, Norway, Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA, VA Boston Hlth Care Syst, Brockton, MA 02301 USA, Natl Univ Ireland Galway, Dept Psychiat, Galway, Ireland, Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH16 4SB, Midlothian, Scotland, Univ Edinburgh, Div Psychiat, Edinburgh EH16 4SB, Midlothian, Scotland, Oslo Univ Hosp, Div Mental Hlth & Addict, N-0424 Oslo, Norway, Beth Israel Deaconess Med Ctr, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02114 USA, Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia, Univ Newcastle, Sch Psychol, Callaghan, NSW 2308, Australia, Med Univ, Psychiat Clin 1, Sofia 1431, Bulgaria, Aarhus Univ Hosp, Dept P, DK-8240 Risskov, Denmark, Royal Coll Surgeons Ireland, Dept Psychiat, Dublin 2, Ireland, Kings Coll London, London SE5 8AF, England, Maastricht Univ, Med Ctr, South Limburg Mental Hlth Res & Teaching Network, EURON, NL-6229 HX Maastricht, Netherlands, Univ Liverpool, Inst Translat Med, Liverpool L69 3BX, Merseyside, England, Max Planck Inst Psychiat, D-80336 Munich, Germany, Munich Cluster Syst Neurol SyNergy, D-80336 Munich, Germany, Jena Univ Hosp, Dept Psychiat & Psychotherapy, D-07743 Jena, Germany, Univ Queensland, Queensland Brain Inst, Dept Psychiat, St Lucia, Qld 4072, Australia, Univ Queensland, Queensland Ctr Mental Hlth Res, St Lucia, Qld 4072, Australia, Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA, Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland, Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA, Umea Univ, Dept Clin Sci, SE-90187 Umea, Sweden, DETECT Early Intervent Serv Psychosis, Blackrock, Dublin, Ireland, Queens Univ Belfast, Inst Clin Sci, Ctr Publ Hlth, Belfast BT12 6AB, Antrim, North Ireland, Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA, Kings Coll London, Inst Psychiat, London SE5 8AF, England, Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic 3053, Australia, Melbourne Hlth, Melbourne, Vic 3053, Australia, Univ Helsinki, Dept Psychiat, FI-00029 Helsinki, Finland, Natl Inst Hlth & Welf, Publ Hlth Genom Unit, FI-00271 Helsinki, Finland, Univ Belgrade, Fac Med, Belgrade 11000, Serbia, Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA, Univ Helsinki, FIMM, FI-00014 Helsinki, Finland, Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA, Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England, Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA, Icahn Sch Med Mt Sinai, Inst Multiscale Biol, New York, NY 10029 USA, Pfizer Worldwide Res & Dev, Pharma Therapeut Clin Res, Cambridge, MA 02139 USA, Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany, Univ Erlangen Nurnberg, Psychiat & Psychotherapy Clin, D-91054 Erlangen, Germany, Hunter New England Hlth Serv, Newcastle, NSW 2308, Australia, Univ Newcastle, Sch Biomed Sci, Newcastle, NSW 2308, Australia, NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA, Univ Iceland, Natl Univ Hosp, Landspitali, IS-101 Reykjavik, Iceland, Tbilisi State Med Univ TSMU, Dept Psychiat & Drug Addict, GE-0177 Tbilisi, Rep of Georgia, Bronx Vet Affairs Med Ctr, New York, NY 10468 USA, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England, deCODE Genet, IS-101 Reykjavik, Iceland, Med Univ Vienna, Dept Clin Neurol, A-1090 Vienna, Austria, Lieber Inst Brain Dev, Baltimore, MD 21205 USA, Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CG Utrecht, Netherlands, Berkshire Healthcare NHS Fdn Trust, Bracknell RG12 1BQ, Berks, England, Univ Verona, Sect Psychiat, I-37134 Verona, Italy, Univ Oulu, Dept Psychiat, Oulu 90014, Finland, Univ Hosp Oulu, Oys 90029, Finland, Royal Coll Surgeons Ireland, Dublin 2, Ireland, Hlth Res Board, Dublin 2, Ireland, Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia, Pfizer Worldwide Res & Dev, Computat Sci CoE, Cambridge, MA 02139 USA, ASTAR, Genome Inst Singapore, Singapore 138672, Singapore, UCL, London WC1E 6BT, England, Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA, Res Ctr Juelich, Inst Neurosci & Med INM 1, D-52428 Julich, Germany, Hebrew Univ Jerusalem, Dept Genet, IL-91905 Jerusalem, Israel, F Hoffmann La Roche & Co Ltd, Pharma Res & Early Dev, Neurosci Discovery & Translat Area, CH-4070 Basel, Switzerland, Univ Western Australia, Sch Psychiat & Clin Neurosci, Ctr Clin Res Neuropsychiat, Perth, WA 6000, Australia, Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23298 USA, Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23298 USA, Feinstein Inst Med Res, Manhasset, NY 11030 USA, Hofstra NS LIJ Sch Med, Hempstead, NY 11549 USA, Zucker Hillside Hosp, Glen Oaks, NY 11004 USA, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore, Univ Queensland, Queensland Ctr Mental Hlth Res, Brisbane, Qld 4076, Australia, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA, Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 Rotterdam, Netherlands, Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Complex Trait Genet, NL-1081 Amsterdam, Netherlands, Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, NL-1081 Amsterdam, Netherlands, Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland, Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21205 USA, Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA, Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD 21205 USA, Johns Hopkins Sch Med, Inst Med Genet, Baltimore, MD 21205 USA, Univ Copenhagen, Dept Clin Med, DK-2200 Copenhagen, Denmarken
dc.identifier.journalNatureen
dc.rights.accessLandspitali Access - LSH-aðganguren
html.description.abstractSchizophrenia 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.


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