Biological insights from 108 schizophrenia-associated genetic loci (original) (raw)
References
- Saha, S., Chant, D. & McGrath, J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch. Gen. Psychiatry 64, 1123–1131 (2007)
Article PubMed Google Scholar - World Health Organization. The Global Burden of Disease: 2004 Update (WHO Press, 2008)
- Knapp, M., Mangalore, R. & Simon, J. The global costs of schizophrenia. Schizophr. Bull. 30, 279–293 (2004)
Article PubMed Google Scholar - Lieberman, J. A. et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353, 1209–1223 (2005)
Article CAS PubMed Google Scholar - Carlsson, A. & Lindqvist, M. Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol. Toxicol. 20, 140–144 (1963)
Article CAS Google Scholar - van Rossum, J. M. The significance of dopamine-receptor blockade for the mechanism of action of neuroleptic drugs. Arch. Int. Pharmacodyn. Ther. 160, 492–494 (1966)
CAS PubMed Google Scholar - Lichtenstein, P. et al. Recurrence risks for schizophrenia in a Swedish national cohort. Psychol. Med. 36, 1417–1425 (2006)
Article PubMed Google Scholar - Sullivan, P. F., Kendler, K. S. & Neale, M. C. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch. Gen. Psychiatry 60, 1187–1192 (2003)
Article PubMed Google Scholar - Sullivan, P. F., Daly, M. J. & O’Donovan, M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nature Rev. Genet. 13, 537–551 (2012)
Article CAS PubMed Google Scholar - International Schizophrenia Consortium. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752 (2009)
- Ripke, S. et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genet. 45, 1150–1159 (2013)
Article CAS PubMed Google Scholar - Ikeda, M. et al. Genome-wide association study of schizophrenia in a Japanese population. Biol. Psychiatry 69, 472–478 (2011)
Article PubMed Google Scholar - Hamshere, M. L. et al. Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC. Mol. Psychiatry 18, 708–712 (2013)
Article CAS PubMed Google Scholar - O’Donovan, M. C. et al. Identification of novel schizophrenia loci by genome-wide association and follow-up. Nature Genet. 40, 1053–1055 (2008)
Article CAS PubMed Google Scholar - Rietschel, M. et al. Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe. Mol. Psychiatry 17, 906–917 (2012)
Article CAS PubMed Google Scholar - Schizophrenia Psychiatric Genome-Wide Association Study Consortium. Genome-wide association study identifies five new schizophrenia loci. Nature Genet. 43, 969–976 (2011)
- Irish Schizophrenia Genomics Consortium & Wellcome Trust Case Control Consortium. Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia. Biol. Psychiatry 72, 620–628 (2012)
- Shi, J. et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 460, 753–757 (2009)
Article ADS CAS PubMed PubMed Central Google Scholar - Shi, Y. et al. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nature Genet. 43, 1224–1227 (2011)
Article CAS PubMed Google Scholar - Stefansson, H. et al. Common variants conferring risk of schizophrenia. Nature 460, 744–747 (2009)
Article ADS CAS PubMed PubMed Central Google Scholar - Steinberg, S. et al. Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Hum. Mol. Genet. 20, 4076–4081 (2011)
Article CAS PubMed PubMed Central Google Scholar - Yue, W. H. et al. Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nature Genet. 43, 1228–1231 (2011)
Article CAS PubMed Google Scholar - Lencz, T. et al. Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder. Nature Commun. 4, 2739 (2013)
Article ADS CAS Google Scholar - Psychiatric GWAS Consortium. A framework for interpreting genomewide association studies of psychiatric disorders. Mol. Psychiatry 14, 10–17 (2009)
- The 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010)
- Begum, F., Ghosh, D., Tseng, G. C. & Feingold, E. Comprehensive literature review and statistical considerations for GWAS meta-analysis. Nucleic Acids Res. 40, 3777–3784 (2012)
Article CAS PubMed PubMed Central Google Scholar - Lango Allen, H. et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832–838 (2010)
Article ADS CAS PubMed PubMed Central Google Scholar - Jostins, L. et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012)
Article CAS PubMed PubMed Central Google Scholar - Yang, J. et al. Genomic inflation factors under polygenic inheritance. Eur. J. Hum. Genet. 19, 807–812 (2011)
Article PubMed PubMed Central Google Scholar - Bulik-Sullivan, B. K. et al. LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Preprint at http://dx.doi.org/10.1101/002931 (2014)
- Ferreira, M. A. et al. Collaborative genome-wide association supports a role for ANK3 and CACNA1C in bipolar disorder. Nature Genet. 40, 1056–1058 (2008)
Article CAS PubMed Google Scholar - Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 1371–1379 (2013)
- Purcell, S. M. et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature. 506, 185–190 (2014)
Article ADS CAS PubMed PubMed Central Google Scholar - Fromer, M. et al. De novo mutations in schizophrenia implicate synaptic networks. Nature. 506, 179–184 (2014)
Article ADS CAS PubMed PubMed Central Google Scholar - Kirov, G. et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol. Psychiatry 17, 142–153 (2012)
Article CAS PubMed Google Scholar - Wellcome Trust Case Control Consortium Bayesian refinement of association signals for 14 loci in 3 common diseases. Nature Genet. 44, 1294–1301 (2012)
Article CAS Google Scholar - Nicolae, D. L. et al. Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet. 6, e1000888 (2010)
Article CAS PubMed PubMed Central Google Scholar - Maurano, M. T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190–1195 (2012)
Article ADS CAS PubMed PubMed Central Google Scholar - Richards, A. L. et al. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain. Mol. Psychiatry 17, 193–201 (2012)
Article CAS PubMed Google Scholar - Wright, F. A. et al. Heritability and genomics of gene expression in peripheral blood. Nature Genet. 46, 430–437 (2014)
Article CAS PubMed Google Scholar - Doyle, J. P. et al. Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell 135, 749–762 (2008)
Article CAS PubMed PubMed Central Google Scholar - Tkachev, D. et al. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 362, 798–805 (2003)
Article CAS PubMed Google Scholar - Benros, M. E., Mortensen, P. B. & Eaton, W. W. Autoimmune diseases and infections as risk factors for schizophrenia. Ann. NY Acad. Sci. 1262, 56–66 (2012)
Article ADS PubMed Google Scholar - Holmans, P. et al. Gene ontology analysis of GWA study data sets provides insights into the biology of bipolar disorder. Am. J. Hum. Genet. 85, 13–24 (2009)
Article CAS PubMed PubMed Central Google Scholar - Lee, P. H., O’Dushlaine, C., Thomas, B. & Purcell, S. InRich: interval-based enrichment analysis for genome-wide association studies. Bioinformatics 28, 1797–1799 (2012)
Article CAS PubMed PubMed Central Google Scholar - Lee, S. H., Goddard, M. E., Wray, N. R. & Visscher, P. M. A better coefficient of determination for genetic profile analysis. Genet. Epidemiol. 36, 214–224 (2012)
Article PubMed Google Scholar - Gottesman, I. I. & Gould, T. D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160, 636–645 (2003)
Article PubMed Google Scholar - Insel, T. et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167, 748–751 (2010)
Article PubMed Google Scholar - Lips, E. S. et al. Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia. Mol. Psychiatry 17, 996–1006 (2012)
Article CAS PubMed Google Scholar - Lewis, B. P., Burge, C. B. & Bartel, D. P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15–20 (2005)
Article CAS PubMed Google Scholar
Acknowledgements
Core funding for the Psychiatric Genomics Consortium is from the US National Institute of Mental Health (U01 MH094421). We thank T. Lehner (NIMH). The work of the contributing groups was supported by numerous grants from governmental and charitable bodies as well as philanthropic donation. Details are provided in the Supplementary Notes. Membership of the Wellcome Trust Case Control Consortium and of the Psychosis Endophenotype International Consortium are provided in the Supplementary Notes.
Author information
Author notes
- Wellcome Trust Case-Control Consortium and Thomas Werge: A list of authors and affiliations appear in the Supplementary Information.
- Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
- University College London, London WC1E 6BT, UK.
Authors and Affiliations
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
Stephan Ripke, Benjamin M. Neale, Kai-How Farh, Phil Lee, Brendan Bulik-Sullivan, Hailiang Huang, Menachem Fromer, Jacqueline I. Goldstein & Mark J. Daly - Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, 02142, Massachusetts, USA
Stephan Ripke, Benjamin M. Neale, Phil Lee, Brendan Bulik-Sullivan, Richard A. Belliveau Jr, Sarah E. Bergen, Elizabeth Bevilacqua, Kimberly D. Chambert, Menachem Fromer, Giulio Genovese, Colm O’Dushlaine, Edward M. Scolnick, Jordan W. Smoller, Steven A. McCarroll, Jennifer L. Moran, Aarno Palotie, Tracey L. Petryshen & Mark J. Daly - Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, 02142, Massachusetts, USA
Benjamin M. Neale, Hailiang Huang, Tune H. Pers, Jacqueline I. Goldstein, Joel N. Hirschhorn, Alkes Price, Eli A. Stahl, Tõnu Esko & Mark J. Daly - Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
Benjamin M. Neale, Phil Lee, Menachem Fromer, Jordan W. Smoller & Aarno Palotie - Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Dublin 8, Ireland.,
Aiden Corvin, Paul Cormican, Gary Donohoe, Derek W. Morris & Michael Gill - MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK.,
James T. R. Walters, Peter A. Holmans, Noa Carrera, Nick Craddock, Valentina Escott-Price, Lyudmila Georgieva, Marian L. Hamshere, David Kavanagh, Sophie E. Legge, Andrew J. Pocklington, Alexander L. Richards, Douglas M. Ruderfer, Nigel M. Williams, George Kirov, Michael J. Owen & Michael C. O’Donovan - National Centre for Mental Health, Cardiff University, Cardiff CF24 4HQ, UK.,
Peter A. Holmans, Nick Craddock, Michael J. Owen & Michael C. O’Donovan - Eli Lilly and Company Limited, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, UK.,
David A. Collier & Younes Mokrab - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London SE5 8AF, UK.,
David A. Collier - Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800, Denmark.,
Tune H. Pers - Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, 02115, Massachusetts, USA
Tune H. Pers, Joel N. Hirschhorn & Tõnu Esko - Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, SE-17176 Stockholm, Sweden.,
Ingrid Agartz, Erik Söderman & Erik G. Jönsson - Department of Psychiatry, Diakonhjemmet Hospital, 0319 Oslo, Norway.,
Ingrid Agartz - NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway.,
Ingrid Agartz, Srdjan Djurovic, Morten Mattingsdal, Ingrid Melle, Ole A. Andreassen & Erik G. Jönsson - Centre for Integrative Register-based Research, CIRRAU, Aarhus University, DK-8210 Aarhus, Denmark.,
Esben Agerbo & Preben B. Mortensen - National Centre for Register-based Research, Aarhus University, DK-8210 Aarhus, Denmark.,
Esben Agerbo & Preben B. Mortensen - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.,
Esben Agerbo, Ditte Demontis, Thomas Hansen, Manuel Mattheisen, Ole Mors, Line Olsen, Henrik B. Rasmussen, Anders D. Børglum, Preben B. Mortensen & Thomas Werge - State Mental Hospital, 85540 Haar, Germany.,
Margot Albus - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 94305, California, USA
Madeline Alexander, Claudine Laurent & Douglas F. Levinson - Department of Psychiatry and Behavioral Sciences, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia 30033, USA.,
Farooq Amin - Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, 30322, Georgia, USA
Farooq Amin - Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, 23298, Virginia, USA
Silviu A. Bacanu, Tim B. Bigdeli, Bradley T. Webb & Brandon K. Wormley - Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen 37075, Germany.,
Martin Begemann, Christian Hammer, Sergi Papiol & Hannelore Ehrenreich - Department of Medical Genetics, University of Pécs, Pécs H-7624, Hungary.,
Judit Bene & Bela Melegh - Szentagothai Research Center, University of Pécs, Pécs H-7624, Hungary.,
Judit Bene & Bela Melegh - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE-17177, Sweden.,
Sarah E. Bergen, Anna K. Kähler, Patrik K. E. Magnusson, Christina M. Hultman & Patrick F. Sullivan - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, 52242, Iowa, USA
Donald W. Black - Department of Psychiatry, University Medical Center Groningen, University of Groningen NL-9700 RB, The Netherlands
Richard Bruggeman - School of Nursing, Louisiana State University Health Sciences Center, New Orleans, 70112, Louisiana, USA
Nancy G. Buccola - Athinoula A. Martinos Center, Massachusetts General Hospital, Boston, 02129, Massachusetts, USA
Randy L. Buckner & Joshua L. Roffman - Center for Brain Science, Harvard University, Cambridge, 02138, Massachusetts, USA
Randy L. Buckner - Department of Psychiatry, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
Randy L. Buckner & Joshua L. Roffman - Department of Psychiatry, University of California at San Francisco, San Francisco, 94143, California, USA
William Byerley - Department of Psychiatry, University Medical Center Utrecht, Rudolf Magnus Institute of Neuroscience, 3584 Utrecht, The Netherlands.,
Wiepke Cahn, René S. Kahn, Eric Strengman & Roel A. Ophoff - Department of Human Genetics, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA
Guiqing Cai & Joseph D. Buxbaum - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA
Guiqing Cai, Kenneth L. Davis, Elodie Drapeau, Joseph I. Friedman, Vahram Haroutunian, Elena Parkhomenko, Abraham Reichenberg, Jeremy M. Silverman & Joseph D. Buxbaum - Centre Hospitalier du Rouvray and INSERM U1079 Faculty of Medicine, 76301 Rouen, France.,
Dominique Campion - Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, 90095, California, USA
Rita M. Cantor & Roel A. Ophoff - Schizophrenia Research Institute, Sydney NSW 2010, Australia.,
Vaughan J. Carr, Stanley V. Catts, Frans A. Henskens, Carmel M. Loughland, Patricia T. Michie, Christos Pantelis, Ulrich Schall, Rodney J. Scott & Assen V. Jablensky - School of Psychiatry, University of New South Wales, Sydney NSW 2031, Australia.,
Vaughan J. Carr - Royal Brisbane and Women’s Hospital, University of Queensland, Brisbane, St Lucia QLD 4072, Australia.,
Stanley V. Catts - Institute of Psychology, Chinese Academy of Science, Beijing, 100101, China
Raymond C. K. Chan - Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Ronald Y. L. Chen, Eric Y. H. Chen, Miaoxin Li, Hon-Cheong So, Emily H. M. Wong & Pak C. Sham - State Key Laboratory for Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Eric Y. H. Chen, Miaoxin Li & Pak C. Sham - Department of Computer Science, University of North Carolina, Chapel Hill, 27514, North Carolina, USA
Wei Cheng - Castle Peak Hospital, Hong Kong, China
Eric F. C. Cheung - Institute of Mental Health, Singapore, 539747, Singapore
Siow Ann Chong, Jimmy Lee Chee Keong, Kang Sim & Mythily Subramaniam - Department of Psychiatry, Washington University, St. Louis, 63110, Missouri, USA
C. Robert Cloninger & Dragan M. Svrakic - Department of Child and Adolescent Psychiatry, Assistance Publique Hopitaux de Paris, Pierre and Marie Curie Faculty of Medicine and Institute for Intelligent Systems and Robotics, Paris 75013, France.,
David Cohen - Blue Note Biosciences, Princeton, 08540, New Jersey, USA
Nadine Cohen - Department of Genetics, University of North Carolina, Chapel Hill, 27599-7264, North Carolina, USA
James J. Crowley, Martilias S. Farrell, Paola Giusti-Rodríguez, Yunjung Kim, Jin P. Szatkiewicz, Stephanie Williams & Patrick F. Sullivan - Department of Psychological Medicine, Queen Mary University of London, London E1 1BB, UK.,
David Curtis - Division of Psychiatry, Molecular Psychiatry Laboratory, University College London, London WC1E 6JJ, UK.,
David Curtis, Jonathan Pimm, Hugh Gurling & Andrew McQuillin - Sheba Medical Center, Tel Hashomer 52621, Israel.,
Michael Davidson & Mark Weiser - Department of Genomics, Life and Brain Center, D-53127 Bonn, Germany.,
Franziska Degenhardt, Stefan Herms, Per Hoffmann, Andrea Hofman, Sven Cichon & Markus M. Nöthen - Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany.,
Franziska Degenhardt, Stefan Herms, Per Hoffmann, Andrea Hofman, Sven Cichon & Markus M. Nöthen - VIB Department of Molecular Genetics, Applied Molecular Genomics Unit, University of Antwerp, B-2610 Antwerp, Belgium.,
Jurgen Del Favero - Centre for Integrative Sequencing, iSEQ, Aarhus University, DK-8000 Aarhus C, Denmark.,
Ditte Demontis, Manuel Mattheisen, Ole Mors & Anders D. Børglum - Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.,
Ditte Demontis, Manuel Mattheisen & Anders D. Børglum - First Department of Psychiatry, University of Athens Medical School, Athens 11528, Greece.,
Dimitris Dikeos & George N. Papadimitriou - Department of Psychiatry, University College Cork, Co. Cork, Ireland.,
Timothy Dinan - Department of Medical Genetics, Oslo University Hospital, 0424 Oslo, Norway.,
Srdjan Djurovic - Cognitive Genetics and Therapy Group, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Co. Galway, Ireland.,
Gary Donohoe & Derek W. Morris - Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, 60637, Illinois, USA
Jubao Duan, Alan R. Sanders & Pablo V. Gejman - Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, 60201, Illinois, USA
Jubao Duan, Alan R. Sanders & Pablo V. Gejman - Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.,
Frank Dudbridge - Department of Child and Adolescent Psychiatry, University Clinic of Psychiatry, Skopje 1000, Republic of Macedonia.,
Naser Durmishi - Department of Psychiatry, University of Regensburg, 93053 Regensburg, Germany.,
Peter Eichhammer - Department of General Practice, Helsinki University Central Hospital, University of Helsinki P.O. Box 20, Tukholmankatu 8 B, FI-00014, Helsinki, Finland,
Johan Eriksson - Folkhälsan Research Center, Helsinki, Finland, Biomedicum Helsinki 1, Haartmaninkatu 8, FI-00290, Helsinki, Finland.,
Johan Eriksson - National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.,
Johan Eriksson & Veikko Salomaa - Translational Technologies and Bioinformatics, Pharma Research and Early Development, F. Hoffman-La Roche, CH-4070 Basel, Switzerland.,
Laurent Essioux - Department of Psychiatry, Georgetown University School of Medicine, 20057, Washington DC, USA
Ayman H. Fanous - Department of Psychiatry, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA.,
Ayman H. Fanous - Departmentof Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, 23298, Virginia, USA
Ayman H. Fanous - Mental Health Service Line, Washington VA Medical Center, 20422, Washington DC, USA
Ayman H. Fanous - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, D-68159 Mannheim, Germany.,
Josef Frank, Sandra Meier, Thomas G. Schulze, Jana Strohmaier, Stephanie H. Witt & Marcella Rietschel - Department of Genetics, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands.,
Lude Franke & Juha Karjalainen - Department of Psychiatry, University of Colorado Denver, Aurora, 80045, Colorado, USA
Robert Freedman & Ann Olincy - Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, 90095, California, USA
Nelson B. Freimer & Roel A. Ophoff - Department of Psychiatry, University of Halle, 06112 Halle, Germany.,
Marion Friedl, Ina Giegling, Annette M. Hartmann, Bettina Konte & Dan Rujescu - Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, New York, USA
Menachem Fromer, Shaun M. Purcell, Panos Roussos, Douglas M. Ruderfer, Eli A. Stahl & Pamela Sklar - Department of Psychiatry, University of Munich, 80336, Munich, Germany.,
Ina Giegling & Dan Rujescu - Departments of Psychiatry and Human and Molecular Genetics, INSERM, Institut de Myologie, Hôpital de la Pitiè-Salpêtrière, Paris 75013, France.,
Stephanie Godard - Mental Health Research Centre, Russian Academy of Medical Sciences, 115522 Moscow, Russia.,
Vera Golimbet - Neuroscience Therapeutic Area, Janssen Research and Development, Raritan, 08869, New Jersey, USA
Srihari Gopal, Dai Wang & Qingqin S. Li - Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, QLD 4072, Australia.,
Jacob Gratten, S. Hong Lee, Naomi R. Wray, Peter M. Visscher & Bryan J. Mowry - Department of Psychiatry, Academic Medical Centre University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.,
Lieuwe de Haan & Carin J. Meijer - Illumina, La Jolla, California, California 92122, USA.,
Mark Hansen - Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, DK-4000, Denmark.,
Thomas Hansen, Line Olsen, Henrik B. Rasmussen & Thomas Werge - Friedman Brain Institute, Icahn School ofMedicine at Mount Sinai, New York, 10029, New York, USA
Vahram Haroutunian, Joseph D. Buxbaum & Pamela Sklar - J. J. Peters VA Medical Center, Bronx, New York, 10468, New York, USA
Vahram Haroutunian - Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle NSW 2308, Australia.,
Frans A. Henskens - School of Electrical Engineering and Computer Science, University of Newcastle, Newcastle NSW 2308, Australia.,
Frans A. Henskens - Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel CH-4058, Switzerland.,
Stefan Herms, Per Hoffmann & Sven Cichon - Department of Genetics, Harvard Medical School, Boston, Massachusetts, Massachusetts 02115, USA.,
Joel N. Hirschhorn, Tõnu Esko & Steven A. McCarroll - Department of Clinical Biochemistry, Section of Neonatal Screening and Hormones, Immunology and Genetics, Statens Serum Institut, Copenhagen DK-2300, Denmark.,
Mads V. Hollegaard & David M. Hougaard - Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi,470-1192, Japan.,
Masashi Ikeda & Nakao Iwata - Department of Psychiatry, Regional Centre for Clinical Research in Psychosis, Stavanger University Hospital, 4011 Stavanger, Norway.,
Inge Joa - Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona 08035, Spain.,
Antonio Julià & Sara Marsal - Centre for Medical Research, The University of Western Australia, Perth WA6009, Australia.,
Luba Kalaydjieva - The Perkins Institute for Medical Research, The University of Western Australia, Perth WA6009, Australia.,
Luba Kalaydjieva & Assen V. Jablensky - Department of Medical Genetics, Medical University, Sofia 1431, Bulgaria.,
Sena Karachanak-Yankova & Draga Toncheva - Department of Psychology, University of Colorado Boulder, Boulder, 80309, Colorado, USA
Matthew C. Keller - Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada.,
James L. Kennedy, Clement C. Zai & Jo Knight - Department of Psychiatry, University of Toronto, Toronto, Ontario M5T 1R8, Canada.,
James L. Kennedy, Clement C. Zai & Jo Knight - Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada.,
James L. Kennedy & Jo Knight - Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia.,
Andrey Khrunin, Svetlana Limborska & Petr Slominsky - Latvian Biomedical Research and Study Centre, Riga, LV-1067, Latvia.,
Janis Klovins & Liene Nikitina-Zake - Department of Psychiatry and Zilkha Neurogenetics Institute, Keck School of Medicine at University of Southern California, Los Angeles, 90089, California, USA
James A. Knowles, Michele T. Pato & Carlos N. Pato - Faculty of Medicine, Vilnius University, LT-01513 Vilnius, Lithuania.,
Vaidutis Kucinskas & Zita Ausrele Kucinskiene - Department of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, 150 06 Prague, Czech Republic.,
Hana Kuzelova-Ptackova & Milan Macek Jr - Department of Child and Adolescent Psychiatry, Pierre and Marie Curie Faculty of Medicine, Paris 75013, France.,
Claudine Laurent - Duke-NUS Graduate Medical School, Singapore 169857.,
Jimmy Lee Chee Keong - Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.,
Bernard Lerer - Centre for Genomic Sciences, The University of Hong Kong, Hong Kong, China
Miaoxin Li & Pak C. Sham - Mental Health Centre and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, China.,
Tao Li & Qiang Wang - Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, 21205, Maryland, USA
Kung-Yee Liang - Department of Psychiatry, Columbia University, New York, 10032, New York, USA
Jeffrey Lieberman & T. Scott Stroup - Priority Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle NSW 2300, Australia.,
Carmel M. Loughland & Ulrich Schall - Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, 70-453 Szczecin, Poland.,
Jan Lubinski - Department of Mental Health and Substance Abuse Services; National Institute for Health and Welfare, P.O. BOX 30, FI-00271 Helsinki, Finland.,
Jouko Lönnqvist & Jaana Suvisaari - National Institute for Health and Welfare, P.O. BOX 30, FI-00271 Helsinki, Finland.,
Jouko Lönnqvist & Jaana Suvisaari - Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, 21205, Maryland, USA
Brion S. Maher - Department of Psychiatry, University of Bonn, D-53127 Bonn, Germany.,
Wolfgang Maier - Centre National de la Recherche Scientifique, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Hôpital de la Pitié Salpêtrière, 75013 Paris, France.,
Jacques Mallet - Department of Genomics Mathematics, University of Bonn, D-53127 Bonn, Germany.,
Manuel Mattheisen - Research Unit, Sørlandet Hospital, 4604 Kristiansand, Norway.,
Morten Mattingsdal - Department of Psychiatry, Harvard Medical School, Boston, 02115, Massachusetts, USA
Robert W. McCarley, Raquelle I. Mesholam-Gately, Larry J. Seidman & Tracey L. Petryshen - VA Boston Health Care System, Brockton, 02301, Massachusetts, USA
Robert W. McCarley - Department of Psychiatry, National University of Ireland Galway, Co. Galway, Ireland
Colm McDonald - Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH16 4SB, UK.,
Andrew M. McIntosh - Division of Psychiatry, University of Edinburgh, Edinburgh EH16 4SB, UK.,
Andrew M. McIntosh & Douglas H. R. Blackwood - Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway.,
Ingrid Melle & Ole A. Andreassen - Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, 02114, Massachusetts, USA
Raquelle I. Mesholam-Gately & Larry J. Seidman - Estonian Genome Center, University of Tartu, Tartu 50090, Estonia.,
Andres Metspalu, Lili Milani, Mari Nelis & Tõnu Esko - School of Psychology, University of Newcastle, Newcastle NSW 2308, Australia.,
Patricia T. Michie - First Psychiatric Clinic, Medical University, Sofia 1431, Bulgaria.,
Vihra Milanova - Department P, Aarhus University Hospital, DK-8240 Risskov, Denmark.,
Ole Mors & Anders D. Børglum - Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland.,
Kieran C. Murphy - King’s College London, London SE5 8AF, UK.,
Robin M. Murray & John Powell - Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, 6229 HX Maastricht, The Netherlands.,
Inez Myin-Germeys & Jim Van Os - Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.,
Bertram Müller-Myhsok - Max Planck Institute of Psychiatry, 80336 Munich, Germany.,
Bertram Müller-Myhsok - Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany.,
Bertram Müller-Myhsok - Department of Psychiatry and Psychotherapy, Jena University Hospital, 07743 Jena, Germany.,
Igor Nenadic - Department of Psychiatry, Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, St Lucia QLD 4072, Australia.,
Deborah A. Nertney - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA
Gerald Nestadt & Ann E. Pulver - Department of Psychiatry, Trinity College Dublin, Dublin 2, Ireland.,
Kristin K. Nicodemus - Eli Lilly and Company,Lilly Corporate Center, Indianapolis, 46285, Indiana, USA
Laura Nisenbaum - Department of Clinical Sciences, Psychiatry, Umeå University, SE-901 87 Umeå, Sweden.,
Annelie Nordin & Rolf Adolfsson - DETECT Early Intervention Service for Psychosis, Blackrock, Co. Dublin, Ireland.,
Eadbhard O’Callaghan - Centre for Public Health, Institute of Clinical Sciences, Queen’s University Belfast, Belfast BT12 6AB, UK.,
F. Anthony O’Neill - Lawrence Berkeley National Laboratory, University of California at Berkeley, Berkeley, 94720, California, USA
Sang-Yun Oh - Institute of Psychiatry, King’s College London, London SE5 8AF, UK.,
Jim Van Os - Melbourne Neuropsychiatry Centre, University of Melbourne & Melbourne Health, Melbourne, Vic 3053, Australia.,
Christos Pantelis - Department of Psychiatry, University of Helsinki, P.O. Box 590, FI-00029 HUS, Helsinki, Finland.,
Tiina Paunio - Public Health Genomics Unit, National Institute for Health and Welfare, P.O. BOX 30, FI-00271 Helsinki, Finland,
Tiina Paunio & Olli Pietiläinen - Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia.,
Milica Pejovic-Milovancevic - Department of Psychiatry, University of North Carolina, Chapel Hill, 27599-7160, North Carolina, USA
Diana O. Perkins & Patrick F. Sullivan - Institute for Molecular Medicine Finland, FIMM, University of Helsinki, P.O. Box 20FI-00014, Helsinki, Finland,
Olli Pietiläinen & Aarno Palotie - Department of Epidemiology, Harvard School of Public Health, Boston, 02115, Massachusetts, USA
Alkes Price - Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK.,
Digby Quested - Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, 23298, Virginia, USA
Mark A. Reimers & Aaron R. Wolen - Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA
Panos Roussos & Pamela Sklar - PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, 02139, Massachusetts, USA
Christian R. Schubert & Jens R. Wendland - Department of Psychiatry and Psychotherapy, University of Gottingen, 37073 Göttingen, Germany.,
Thomas G. Schulze - Psychiatry and Psychotherapy Clinic, University of Erlangen, 91054 Erlangen, Germany.,
Sibylle G. Schwab - Hunter New England Health Service, Newcastle NSW 2308, Australia.,
Rodney J. Scott - School of Biomedical Sciences, University of Newcastle, Newcastle NSW 2308, Australia.,
Rodney J. Scott - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, 20892, Maryland, USA
Jianxin Shi - University of Iceland, Landspitali, National University Hospital, 101 Reykjavik, Iceland.,
Engilbert Sigurdsson - Department of Psychiatry and Drug Addiction, Tbilisi State Medical University (TSMU), N33, 0177 Tbilisi, Georgia.,
Teimuraz Silagadze - Research and Development, Bronx Veterans Affairs Medical Center, New York, 10468, New York, USA
Jeremy M. Silverman - Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.,
ChrisC. A. Spencer - deCODE Genetics, 101 Reykjavik, Iceland.,
Hreinn Stefansson, Stacy Steinberg & Kari Stefansson - Department of Clinical Neurology, Medical University of Vienna, 1090 Wien, Austria.,
Elisabeth Stogmann & Fritz Zimprich - Lieber Institute for Brain Development, Baltimore, 21205, Maryland, USA
Richard E. Straub & Daniel R. Weinberger - Department of Medical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.,
Eric Strengman - Berkshire Healthcare NHS Foundation Trust, Bracknell RG12 1BQ, UK.,
Srinivas Thirumalai - Section of Psychiatry, University of Verona, 37134 Verona, Italy.,
Sarah Tosato - Department of Psychiatry, University of Oulu, P.O. Box 5000, 90014, Finland.,
Juha Veijola - University Hospital of Oulu, P.O. Box 20, 90029 OYS, Finland.,
Juha Veijola - Health Research Board, Dublin 2, Ireland.,
Dermot Walsh - School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth WA6009, Australia.,
Dieter B. Wildenauer & Assen V. Jablensky - Computational Sciences CoE, Pfizer Worldwide Research and Development, Cambridge, 02139, Massachusetts, USA
Hualin Simon Xi - Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672.,
Jianjun Liu - Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA
Joseph D. Buxbaum - Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, 52428 Juelich, Germany.,
Sven Cichon - Department of Genetics, The Hebrew University of Jerusalem, 91905 Jerusalem, Israel.,
Ariel Darvasi - Neuroscience Discovery and Translational Area, Pharma Research and Early Development, F. Hoffman-La Roche, CH-4070 Basel, Switzerland.,
Enrico Domenici - Centre for Clinical Research in Neuropsychiatry, School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Medical Research Foundation Building, Perth WA6000, Australia.,
Assen V. Jablensky - Departments of Psychiatry and Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, 23298, Virginia, USA
Kenneth S. Kendler & Brien P. Riley - The Feinstein Institute for Medical Research, Manhasset, 11030, New York, USA
Todd Lencz & Anil K. Malhotra - The Hofstra NS-LIJ School of Medicine, Hempstead, 11549, New York, USA
Todd Lencz & Anil K. Malhotra - The Zucker Hillside Hospital, Glen Oaks, 11004, New York, USA
Todd Lencz & Anil K. Malhotra - Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore.,
Jianjun Liu - Queensland Centre for Mental Health Research, University of Queensland, Brisbane 4076, Queensland, Australia.,
Bryan J. Mowry - Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
Tracey L. Petryshen - Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000, The Netherlands.,
Danielle Posthuma - Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, Amsterdam 1081, The Netherlands.,
Danielle Posthuma - Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam 1081, The Netherlands.,
Danielle Posthuma - University of Aberdeen, Institute of Medical Sciences, Aberdeen AB25 2ZD, UK.,
David St Clair - Departments of Psychiatry, Neurology, Neuroscience and Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, 21205, Maryland, USA
Daniel R. Weinberger - Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark.,
Thomas Werge
Consortia
Schizophrenia Working Group of the Psychiatric Genomics Consortium
- Stephan Ripke
- , Benjamin M. Neale
- , Aiden Corvin
- , James T. R. Walters
- , Kai-How Farh
- , Peter A. Holmans
- , Phil Lee
- , Brendan Bulik-Sullivan
- , David A. Collier
- , Hailiang Huang
- , Tune H. Pers
- , Ingrid Agartz
- , Esben Agerbo
- , Margot Albus
- , Madeline Alexander
- , Farooq Amin
- , Silviu A. Bacanu
- , Martin Begemann
- , Richard A. Belliveau Jr
- , Judit Bene
- , Sarah E. Bergen
- , Elizabeth Bevilacqua
- , Tim B. Bigdeli
- , Donald W. Black
- , Richard Bruggeman
- , Nancy G. Buccola
- , Randy L. Buckner
- , William Byerley
- , Wiepke Cahn
- , Guiqing Cai
- , Dominique Campion
- , Rita M. Cantor
- , Vaughan J. Carr
- , Noa Carrera
- , Stanley V. Catts
- , Kimberly D. Chambert
- , Raymond C. K. Chan
- , Ronald Y. L. Chen
- , Eric Y. H. Chen
- , Wei Cheng
- , Eric F. C. Cheung
- , Siow Ann Chong
- , C. Robert Cloninger
- , David Cohen
- , Nadine Cohen
- , Paul Cormican
- , Nick Craddock
- , James J. Crowley
- , David Curtis
- , Michael Davidson
- , Kenneth L. Davis
- , Franziska Degenhardt
- , Jurgen Del Favero
- , Ditte Demontis
- , Dimitris Dikeos
- , Timothy Dinan
- , Srdjan Djurovic
- , Gary Donohoe
- , Elodie Drapeau
- , Jubao Duan
- , Frank Dudbridge
- , Naser Durmishi
- , Peter Eichhammer
- , Johan Eriksson
- , Valentina Escott-Price
- , Laurent Essioux
- , Ayman H. Fanous
- , Martilias S. Farrell
- , Josef Frank
- , Lude Franke
- , Robert Freedman
- , Nelson B. Freimer
- , Marion Friedl
- , Joseph I. Friedman
- , Menachem Fromer
- , Giulio Genovese
- , Lyudmila Georgieva
- , Ina Giegling
- , Paola Giusti-Rodríguez
- , Stephanie Godard
- , Jacqueline I. Goldstein
- , Vera Golimbet
- , Srihari Gopal
- , Jacob Gratten
- , Lieuwe de Haan
- , Christian Hammer
- , Marian L. Hamshere
- , Mark Hansen
- , Thomas Hansen
- , Vahram Haroutunian
- , Annette M. Hartmann
- , Frans A. Henskens
- , Stefan Herms
- , Joel N. Hirschhorn
- , Per Hoffmann
- , Andrea Hofman
- , Mads V. Hollegaard
- , David M. Hougaard
- , Masashi Ikeda
- , Inge Joa
- , Antonio Julià
- , René S. Kahn
- , Luba Kalaydjieva
- , Sena Karachanak-Yankova
- , Juha Karjalainen
- , David Kavanagh
- , Matthew C. Keller
- , James L. Kennedy
- , Andrey Khrunin
- , Yunjung Kim
- , Janis Klovins
- , James A. Knowles
- , Bettina Konte
- , Vaidutis Kucinskas
- , Zita Ausrele Kucinskiene
- , Hana Kuzelova-Ptackova
- , Anna K. Kähler
- , Claudine Laurent
- , Jimmy Lee Chee Keong
- , S. Hong Lee
- , Sophie E. Legge
- , Bernard Lerer
- , Miaoxin Li
- , Tao Li
- , Kung-Yee Liang
- , Jeffrey Lieberman
- , Svetlana Limborska
- , Carmel M. Loughland
- , Jan Lubinski
- , Jouko Lönnqvist
- , Milan Macek Jr
- , Patrik K. E. Magnusson
- , Brion S. Maher
- , Wolfgang Maier
- , Jacques Mallet
- , Sara Marsal
- , Manuel Mattheisen
- , Morten Mattingsdal
- , Robert W. McCarley
- , Colm McDonald
- , Andrew M. McIntosh
- , Sandra Meier
- , Carin J. Meijer
- , Bela Melegh
- , Ingrid Melle
- , Raquelle I. Mesholam-Gately
- , Andres Metspalu
- , Patricia T. Michie
- , Lili Milani
- , Vihra Milanova
- , Younes Mokrab
- , Derek W. Morris
- , Ole Mors
- , Kieran C. Murphy
- , Robin M. Murray
- , Inez Myin-Germeys
- , Bertram Müller-Myhsok
- , Mari Nelis
- , Igor Nenadic
- , Deborah A. Nertney
- , Gerald Nestadt
- , Kristin K. Nicodemus
- , Liene Nikitina-Zake
- , Laura Nisenbaum
- , Annelie Nordin
- , Eadbhard O’Callaghan
- , Colm O’Dushlaine
- , F. Anthony O’Neill
- , Sang-Yun Oh
- , Ann Olincy
- , Line Olsen
- , Jim Van Os
- , Psychosis Endophenotypes International Consortium
- , Christos Pantelis
- , George N. Papadimitriou
- , Sergi Papiol
- , Elena Parkhomenko
- , Michele T. Pato
- , Tiina Paunio
- , Milica Pejovic-Milovancevic
- , Diana O. Perkins
- , Olli Pietiläinen
- , Jonathan Pimm
- , Andrew J. Pocklington
- , John Powell
- , Alkes Price
- , Ann E. Pulver
- , Shaun M. Purcell
- , Digby Quested
- , Henrik B. Rasmussen
- , Abraham Reichenberg
- , Mark A. Reimers
- , Alexander L. Richards
- , Joshua L. Roffman
- , Panos Roussos
- , Douglas M. Ruderfer
- , Veikko Salomaa
- , Alan R. Sanders
- , Ulrich Schall
- , Christian R. Schubert
- , Thomas G. Schulze
- , Sibylle G. Schwab
- , Edward M. Scolnick
- , Rodney J. Scott
- , Larry J. Seidman
- , Jianxin Shi
- , Engilbert Sigurdsson
- , Teimuraz Silagadze
- , Jeremy M. Silverman
- , Kang Sim
- , Petr Slominsky
- , Jordan W. Smoller
- , Hon-Cheong So
- , ChrisC. A. Spencer
- , Eli A. Stahl
- , Hreinn Stefansson
- , Stacy Steinberg
- , Elisabeth Stogmann
- , Richard E. Straub
- , Eric Strengman
- , Jana Strohmaier
- , T. Scott Stroup
- , Mythily Subramaniam
- , Jaana Suvisaari
- , Dragan M. Svrakic
- , Jin P. Szatkiewicz
- , Erik Söderman
- , Srinivas Thirumalai
- , Draga Toncheva
- , Sarah Tosato
- , Juha Veijola
- , John Waddington
- , Dermot Walsh
- , Dai Wang
- , Qiang Wang
- , Bradley T. Webb
- , Mark Weiser
- , Dieter B. Wildenauer
- , Nigel M. Williams
- , Stephanie Williams
- , Stephanie H. Witt
- , Aaron R. Wolen
- , Emily H. M. Wong
- , Brandon K. Wormley
- , Hualin Simon Xi
- , Clement C. Zai
- , Xuebin Zheng
- , Fritz Zimprich
- , Naomi R. Wray
- , Kari Stefansson
- , Peter M. Visscher
- , Wellcome Trust Case-Control Consortium
- , Rolf Adolfsson
- , Ole A. Andreassen
- , Douglas H. R. Blackwood
- , Elvira Bramon
- , Joseph D. Buxbaum
- , Anders D. Børglum
- , Sven Cichon
- , Ariel Darvasi
- , Enrico Domenici
- , Hannelore Ehrenreich
- , Tõnu Esko
- , Pablo V. Gejman
- , Michael Gill
- , Hugh Gurling
- , Christina M. Hultman
- , Nakao Iwata
- , Assen V. Jablensky
- , Erik G. Jönsson
- , Kenneth S. Kendler
- , George Kirov
- , Jo Knight
- , Todd Lencz
- , Douglas F. Levinson
- , Qingqin S. Li
- , Jianjun Liu
- , Anil K. Malhotra
- , Steven A. McCarroll
- , Andrew McQuillin
- , Jennifer L. Moran
- , Preben B. Mortensen
- , Bryan J. Mowry
- , Markus M. Nöthen
- , Roel A. Ophoff
- , Michael J. Owen
- , Aarno Palotie
- , Carlos N. Pato
- , Tracey L. Petryshen
- , Danielle Posthuma
- , Marcella Rietschel
- , Brien P. Riley
- , Dan Rujescu
- , Pak C. Sham
- , Pamela Sklar
- , David St Clair
- , Daniel R. Weinberger
- , Jens R. Wendland
- , Thomas Werge
- , Mark J. Daly
- , Patrick F. Sullivan
- & Michael C. O’Donovan
Contributions
The individual studies or consortia contributing to the GWAS meta-analysis were led by R.A., O.A.A., D.H.R.B., A.D.B., E. Bramon, J.D.B., A.C., D.A.C., S.C., A.D., E. Domenici, H.E., T.E., P.V.G., M.G., H.G., C.M.H., N.I., A.V.J., E.G.J., K.S.K., G.K., J. Knight, T. Lencz, D.F.L., Q.S.L., J. Liu, A.K.M., S.A.M., A. McQuillin, J.L.M., P.B.M., B.J.M., M.M.N., M.C.O’D., R.A.O., M.J.O., A. Palotie, C.N.P., T.L.P., M.R., B.P.R., D.R., P.C.S, P. Sklar. D.St.C., P.F.S., D.R.W., J.R.W., J.T.R.W. and T.W. Together with the core statistical analysis group led by M.J.D. comprising S.R., B.M.N. and P.A.H., this group comprised the management group led by M.C.O’D. who were responsible for the management of the study and the overall content of the manuscript. Additional analyses and interpretations were contributed by E.A., B.B.-S., D.K., K.-H.F., M. Fromer, H.H., P.L., P.B.M., S.M.P., T.H.P., N.R.W. and P.M.V. The phenotype supervisory group comprised A.C., A.H.F., P.V.G., K.K.K. and B.J.M. D.A.C. led the candidate selected genes subgroup comprised of M.J.D., E. Dominici, J.A.K., A.M.H., M.C.O’D, B.P.R., D.R., E.M.S. and P. Sklar. Replication results were provided by S.S., H.S. and K.S. The remaining authors contributed to the recruitment, genotyping, or data processing for the contributing components of the meta-analysis. A.C., M.J.D., B.M.N., S.R., P.F.S. and M.C.O’D. took responsibility for the primary drafting of the manuscript which was shaped by the management group. All other authors saw, had the opportunity to comment on, and approved the final draft.
Corresponding author
Correspondence toMichael C. O’Donovan.
Ethics declarations
Competing interests
CFI statement–Several of the authors are employees of the following pharmaceutical companies; Pfizer (C.R.S., J.R.W., H.S.X.), F.Hoffman-La Roche (E.D., L.E.), Eli Lilly (D.A.C., Y.M., L.N.) and Janssen (S.G., D.W., Q.S.L.; also N.C. an ex-employee). Others are employees of deCODE genetics (S.S, H.S., K.S.). None of these companies influenced the design of the study, the interpretation of the data, or the amount of data reported, or financially profit by publication of the results which are pre-competitive. The other authors declare no competing interests.
Additional information
Results can be downloaded from the Psychiatric Genomics Consortium website (http://pgc.unc.edu) and visualized using Ricopili (http://www.broadinstitute.org/mpg/ricopili). Genotype data for the samples where the ethics permit deposition are available upon application from the NIMH Genetics Repository (https://www.nimhgenetics.org).
A list of authors and affiliations appear in the Supplementary Information.
Extended data figures and tables
Extended Data Figure 1 Homogeneity of effects across studies.
Plot of the first two principal components (PCs) from principal components analysis (PCA) of the logistic regression β coefficients for autosomal genome-wide significant associations. The input data were the β coefficients from 52 samples for 112 independent SNP associations (excluding 3 chrX SNPs and 13 SNPs with missing values in Asian samples). PCAs were weighted by the number of cases. Each circle shows the location of a study on PC1 and PC2. Circle size and colour are proportional to the number of cases in each sample (larger and darker red circles correspond to more cases). Most samples cluster. Outliers had either small numbers of cases (‘small’) or were genotyped on older arrays. Abbreviations: a500 (Affymetrix 500K); a5 (Affymetrix 5.0). Studies that did not use conventional research interviews are in the central cluster (CLOZUK, Sweden, and Denmark-Aarhus studies, see Supplementary Methods for sample descriptions).
Extended Data Figure 2 Quantile-quantile plot.
Quantile-quantile plot of the discovery genome-wide association meta-analysis of 49 case control samples (34,241 cases and 45,604 controls) and 3 family based association studies (1,235 parent affected-offspring trios). Expected –log10 P values are those expected under the null hypothesis. Observed are the GWAS association results derived by logistic regression (2-tailed) as in Fig. 1. For clarity, we avoided expansion of the y axis by setting the smallest association P values to 10−12. The shaded area surrounded by a red line indicates the 95% confidence interval under the null. λGC is the observed median χ2 test statistic divided by the median expected χ2 test statistic under the null hypothesis.
Extended Data Figure 3 Linkage disequilibrium score regression consistent with polygenic inheritance.
The relationship between marker χ_2_ association statistics and linkage disequilibrium (LD) as measured by the linkage disequilibrium score. Linkage disequilibrium score is the sum of the r_2 values between a variant and all other known variants within a 1 cM window, and quantifies the amount of genetic variation tagged by that variant. Variants were grouped into 50 equal-sized bins based on linkage disequilibrium score rank. Linkage disequilibrium score bin and mean χ_2 denotes mean linkage disequilibrium score and test statistic for markers each bin. a, b, We simulated (Supplementary Methods) test statistics under two scenarios: a, no true association, inflation due to population stratification; and b, polygenic inheritance (λ = 1.32), in which we assigned independent and identically distributed per-normalized-genotype effects to a randomly selected subset of variants. c, Results from the PGC schizophrenia GWAS (λ = 1.48). The real data are strikingly similar to the simulated data summarized in b but not a. The intercept estimates the inflation in the mean χ_2_ that results from confounding biases, such as cryptic relatedness or population stratification. Thus, the intercept of 1.066 for the schizophrenia GWAS suggests that ∼90% of the inflation in the mean χ_2_ results from polygenic signal. The results of the simulations are also consistent with theoretical expectation (see Supplementary Methods). λ is the median χ2 test statistic from the simulations (a, b) or the observed data (c) divided by the median expected χ2 test statistic under the null hypothesis.
Extended Data Figure 4 Enrichment of associations in tissues and cells.
Genes whose transcriptional start is nearest to the most associated SNP at each schizophrenia-associated locus were tested for enriched expression in purified brain cell subsets obtained from mouse ribotagged lines41 using enrichment analysis described in the Supplementary Methods. The red dotted line indicates P = 0.05.
Extended Data Figure 5 MGS risk profile score analysis.
Polygenic risk profile score (RPS) analyses using the MGS18 sample as target, and deriving risk alleles from three published schizophrenia data sets (x axis): ISC (2,615 cases and 3,338 controls)10, PGC1 (excluding MGS, 9,320 cases and 10,228 controls)16, and the current meta-analysis (excluding MGS) with 32,838 cases and 44,357 controls. Samples sizes differ slightly from the original publications due to different analytical procedures. This shows the increasing RPS prediction with increasing training data set size reflecting improved precision of estimates of the SNP effect sizes. The proportion of variance explained (y axis; Nagelkerke’s _R_2) was computed by comparison of a full model (covariates + RPS) score to a reduced model (covariates only). Ten different P value thresholds (_P_T) for selecting risk alleles are denoted by the colour of each bar (legend above plot). For significance testing, see the bottom legend which denotes the P value for the test that _R_2 is different from zero. All numerical data and methods used to generate these plots are available in Supplementary Table 6 and Supplementary Methods.
Extended Data Figure 6 Risk profile score analysis.
We defined 40 target subgroups of the primary GWAS data set and performed 40 leave-one-out GWAS analyses (see Supplementary Methods and Supplementary Table 7) from which we derived risk alleles for RPS analysis (x axis) for each target subgroup. a, The proportion of variance explained (y axis; Nagelkerke’s _R_2) was computed for each target by comparison of a full model (covariates + RPS) score to a reduced model (covariates only). For clarity, 3 different P value thresholds (_P_T) are presented denoted by the colour of each bar (legend above plot) as for Extended Data Fig. 5, but for clarity we restrict to fewer P value thresholds (_P_T of 5 × 10−8, 1 × 10−4 and 0.05) and removed the significance values. b, The proportion of variance on the liability scale from risk scores calculated at the _P_T 0.05 with 95% CI bar assuming baseline population disease risk of 1%. c, Area under the receiver operating curve (AUC). All numerical data and methods used to generate these plots are available in Supplementary Table 7 and Supplementary Methods.
Extended Data Table 1 ALIGATOR and INRICH
Extended Data Table 2 de novo overlap
Supplementary information
Supplementary Information
This file contains Supplementary Text, Supplementary Tables 1-3, Supplementary References and Supplementary Notes (including a list of consortium members and acknowledgements) – see contents page for details. (PDF 1772 kb)
Supplementary Figure
This file contains Supplementary Figure 1. (PDF 2168 kb)
Supplementary Table 4
Credible causal schizophrenia SNPs, coding variants, and eQTLs. Worksheet 1: Coding variants: Index SNP is the schizophrenia associated SNP defining the schizophrenia associated region. Coding variant, R2, and gene denotes a coding credible SNP and the R2 with the index SNP, and the gene containing the coding variant. CHR (chromosome), BP (base position), A1A2 (alleles 1 and 2), frequencies of allele 1 (FRQ_A1), INFO (imputation quality) and P (P-value) refer to the index SNP in the discovery GWAS. P (incl rep) refers to replication P value for index SNP. Worksheets 2 and 3: Brain and blood eQTL: Credible SNP denotes a SNP within the schizophrenia credible set (defined in supplementary material) that is also a cis eQTL (transcript within 1Mb, PeQTL<1x10-4). P(cSCZ) is the schizophrenia (discovery) GWAS association P-value for the credible SNP. The Prob(cSCZ) is the normalized probability of the credible variant being causal for schizophrenia. N(cSCZ) is the number of variants in the credible set of schizophrenia variants within a region spanned by eQTLs at P<10-4. eQTL SNP is the most significant expression associated SNP in the region for the gene in next column (N.B., many regions have an eQTL for more than 1 gene). eQTLgene is the gene that is linked to the eQTL SNP. P(eQTL) is the association P-value between the eQTL SNP and the eQTLgene in the previous two columns. Prob(eQTL) is the normalized probability that the eQTL SNP is also the causal SNP for schizophrenia (high values mean higher probability of being causal). eQTLcumsum is the cumulative sum of the probability of all SNPs into the region, up to the inclusion of the max eQTL in locus ordered by probability of being the functional SNP. PeQTL(SCZ) is the schizophrenia association P-value for the eQTL SNP. R2 (cSCZ/ eQTL) is the R2 between the credibleSNP and eQTL SNP. Associations to schizophrenia that are plausibly explained by an eQTL are in bold. Separate worksheets provide information on brain and blood eQTL analyses. Distinct loci are alternately shaded/unshaded. (XLSX 106 kb)
Supplementary Table 5
Pathway analyses by ALIGATOR and INRICH. Enrichment analyses using ALIGATOR and INRICH were performed as described in Supplementary Text. Pathway ID denotes the pathway source: GO (Gene ontology; http://www.geneontology.org), KEGG (Kyoto Encyclopaedia of Genes and Genomes; http://www.genome.jp/kegg), PAN-PW (PANTHER; http://www.pantherdb.org/pathway), Reactome (http://www.reactome.org/download), BioCarta (downloaded from the Molecular Signatures Database v4.0 http://www.broadinstitute.org/gsea/msigdb/index.jsp), MGI (Mouse Genome Informatics; http://www.informatics.jax.org), and NCI pathways (NCI: http://pid.nci.nih.gov). (XLS 173 kb)
Supplementary Table 7
Risk Profile Score Analyses. Risk Profile Score (RPS) analysis was performed as described in supplementary text. RPS datasets tab provides the name given for sample in which RPS was performed (target label) and the datasets included (defined in Supplementary Table 1). The GWAS data used to define the risk alleles for RPS analysis represents the remaining GWAS samples. For various GWAS P-value thresholds (denoted PT), we calculated: 1) the significance of the case-control score difference was analyzed (P tab), 2) the proportion of variance explained (Nagelkerke’s R2, R2 tab), 3) the proportion of variance on the liability scale explained by RPS (h2I tab) with standard error in brackets, 4) area under the receiver operator characteristic curve (AUC tab), and 5) odds ratio for the 10th RPS decile group compared with lowest decile with confidence interval in brackets. Ncases tab denotes number of cases in each target set. (XLS 96 kb)
Supplementary Table 6
RPS analysis of MGS sample. Risk Profile Score (RPS) analyses was performed using the MGS dataset as target, using three distinct published results for SCZ GWAS, from the (1) ISC (2009) study of 2615 cases and 3338 controls11 (denoted ISC columns) (2) PGC1 (excluding MGS, denoted PGC1 columns) with 9320 cases and 10228 controls22, (3) current meta analysis (excluding MGS, denoted Current columns) with 32838 cases and 44357 controls. For various GWAS P value thresholds (denoted PT), we calculated 1) the significance of the case-control score difference was analyzed (P tab) 2) The proportion of variance explained (Nagelkerke’s R2, R2 tab) 3) The proportion of variance on the liability scale explained by RPS (h2I tab) with standard error in brackets 4) Area under the receiver operator characteristic curve (AUC tab) and 5) Odds ratio for 10th RPS decile group compared with lowest decile with confidence interval in brackets. Ncases tab denotes number of cases in each target set. (XLS 32 kb)
PowerPoint slides
Rights and permissions
About this article
Cite this article
Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci.Nature 511, 421–427 (2014). https://doi.org/10.1038/nature13595
- Received: 06 March 2014
- Accepted: 18 June 2014
- Published: 22 July 2014
- Issue Date: 24 July 2014
- DOI: https://doi.org/10.1038/nature13595