About SCHEMA

The Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium is a large multi-site collaboration dedicated to aggregating, generating, and analyzing high-throughput sequencing data of schizophrenia patients to improve our understanding of disease architecture and advance gene discovery. The consortium was formed in the summer of 2017 with a commitment of data sharing, diversity, and inclusivity - our hope is that the findings from this study and others like it will provide a foundation for further investigation of disease mechanism and therapeutic discovery. This browser is part of that overall effort to display and share these results with the wider scientific community.

The SCHEMA Phase I dataset (GRCh37/hg19) contains the analysis of exomes from 24,248 cases and 97,322 controls, and de novo mutations from 3,402 parent-proband trios. Our study has actively recruited from diverse global populations, and includes individuals of European, Latin American, East Asian, Ashkenazi Jewish, and African American ancestry. Because the sequence data was generated with various capture technologies over a span of seven years, we adapted and developed methods to reduce possible confounders, and incorporated this information during the quality control and analysis steps. The first results have provided genome-wide significant results associating ultra-rare protein-coding variants in individual genes to risk of schizophrenia. Later releases are planned with larger number of samples that will further increase power, and will be released here before any publication.

We would like to thank the many tens of thousands of patients and families who generously contributed to our effort. This project is made possible by the generosity of many funders, including the Stanley Family Foundation, National Institutes of Mental Health (NIMH), National Human Genome Research Institute (NHGRI), Kent and Elizabeth Dauten Foundation, the Dalio Foundation, and the leadership of its members.

Contributing scientists

Tarjinder Singh1,2, Timothy Poterba1,2, David Curtis3,4, Huda Akil5, Mariam Al Eissa6, Jack D. Barchas5, Nicholas Bass6, Tim B. Bigdeli7, Gerome Breen8, Evelyn J. Bromet9, Peter F. Buckley10, William E. Bunney11,12, Jonas Bybjerg-Grauholm13, William F. Byerley5,14, Sinéad B. Chapman2, Wei J. Chen15, Claire Churchhouse1,2, Nicholas Craddock16, Charles Curtis8, Caroline M. Cusick2, Lynn DeLisi5, Sheila Dodge17, Michael A. Escamilla18, Saana Eskelinen19,20, Ayman H. Fanous21, Stephen V. Faraone22, Alessia Fiorentino6, Laurent Francioli1,23, Stacey B. Gabriel17, Diane Gage2, Sarah A. Gagliano Taliun24, Andrea Ganna1,25, Giulio Genovese2, David C. Glahn26, Jakob Grove27, Mei-Hua Hall28, Eija Hämäläinen25, Henrike O. Heyne1,2,29, Matti Holi30, David M. Hougaard13, Daniel P. Howrigan1,2, Hailiang Huang1,2, Hai-Gwo Hwu31, René S. Kahn32,33, Hyun Min Kang24, Konrad J. Karczewski1,2, George Kirov34, James A. Knowles35, Francis S. Lee11,36, Douglas S. Lehrer37, Francesco Lescai38,39, Dolores Malaspina32, Stephen R. Marder32, Steven A. McCarroll2,40, Helena Medeiros21, Lili Milani41, Christopher P. Morley42, Derek W. Morris43, Preben Bo Mortensen44, Richard M. Myers11,45, Merete Nordentoft46,47, Niamh L. O'Brien6, Ana Maria Olivares2, Dost Ongur28, Willem H. Ouwehand48, Duncan S. Palmer1,2, Tiina Paunio49, Digby Quested50, Mark H. Rapaport51, Elliott Rees34, Brandi Rollins11,12, F. Kyle Satterstrom2,52, Alan Schatzberg5, Edward Scolnick2, Laura J. Scott24, Sally I. Sharp6, Pamela Sklar, Jordan W. Smoller53,54, Janet l. Sobell55, Matthew Solomonson23, Christine R. Stevens2,23, Jaana Suvisaari56, Grace Tiao23, Stanley J. Watson57, Nicholas A. Watts23, Douglas H Blackwood58, Anders D. Børglum59,60, Bruce M. Cohen28, Aiden P. Corvin61, Tõnu Esko41, Nelson B. Freimer62, Stephen J. Glatt22, Christina M. Hultman63, Andrew McQuillin6, Aarno Palotie23,25, Carlos N. Pato7, Michele T. Pato7, Ann E. Pulver64, David St. Clair65, Ming T. Tsuang66, Marquis P. Vawter11,67, James T. Walters34, Thomas M. Werge68,69,70,71, Roel A. Ophoff62,72, Patrick F. Sullivan73,74, Michael J. Owen34, Michael Boehnke24, Michael C. O'Donovan34, Benjamin M. Neale1,2,23, Mark J. Daly1,2,23,25

1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA 2Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA 3UCL Genetics Institute, University College London, UK 4Centre for Psychiatry, Queen Mary University London, UK 5Pritzker Neuropsychiatric Disorders Research Consortium 6Division of Psychiatry, University College London, UK 7Department of Psychiatry & Behavioral Sciences, SUNY Downstate College of Medicine, Brooklyn, New York, USA 8Social Genetic and Developmental Psychiatry; Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 8AF, UK 9Department of Psychiatry and Behavioural Health, Stony Brook University, HSC, Level T-10, Stony Brook, New York, USA 10Department of Psychiatry, Virginia Commonwealth University, 1201 E Marshall St., Richmond, Virginia, USA 11Pritzker Neuropsychiatric Disorders Research Consortium 12University of California, Irvine, Department of Psychiatry and Human Behavior 13iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. 14Department of Psychiatry, University of California, SF, California, USA 15College of Public Health; National Taiwan University; Taipei, Taiwan 16National Centre for Mental Health, Cardiff University, UK 17Genomics Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA 18Texas Tech University Health Sciences Center El Paso, Texas, USA 19Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland 20Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland 21Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, New York, USA 22Department of Psychiatry and Behavioral Sciences; SUNY Upstate Medical University; Syracuse, New York, USA 23Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA 24Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA 25Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland 26Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts, USA 27Department of Biomedicine and iSEQ, Center for Integrative Sequencing, Aarhus University, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Center for Genomics and Personalized Medicine, CGPM, Aarhus, Denmark; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark 28McLean Hospital/Harvard Medical School, Belmont, Massachusetts, USA 29Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland" 30Department of Psychiatry, Helsinki University Hospital, Helsinki University, Helsinki, Finland 31Department of Psychiatry; National Taiwan University; Taipei, Taiwan 32Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA 33MIRECC, JP Peters VA Hospital, Bronx, NY 34MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK. 35Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, USA. 36Weill Cornell Medical College, New York, New York, USA 37Department of Psychiatry, Wright State University, 3640 Colonel Gleen Hwy, Dayton, Ohio, USA 38Department of Biomedicine, Aarhus University, Denmark; 39iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark 40Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA 41Institute of Genomics, University of Tartu, Estonia 42Departments of Public Health and Preventive Medicine, Family Medicine, and Psychiatry and Behavioral Sciences, State University of New York, Upstate Medical University, Syracuse, New York, USA 43National University Ireland, Galway, Ireland 44Aarhus University, Denmark 45HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806 46Copenhagen Research Center for Mental Health, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark 47Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark. 48University of Cambridge, Cambridge, UK 49Department of Psychiatry, University of Helsinki, Helsinki, Finland 50Oxford Health NHS Foundation Trust, Oxford, UK 51Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA 52Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA 53Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA 54Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA 55Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA 56Finnish Institute for Health and Welfare, Helsinki, Finland 57Department of Psychiatry, Michigan Neuroscience Institute, Medical School, University of Michigan, Michigan, USA 58University of Edinburgh, Edinburgh, UK 59Department of Biomedicine and iSEQ, Center for Integrative Sequencing, Aarhus University, Denmark 60iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Center for Genomics and Personalized Medicine, CGPM, Aarhus, Denmark 61Trinity College Dublin, Dublin, Ireland 62Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA 63Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 64School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA 65University of Aberdeen, Aberdeen, UK 66Center for Behavioral Genomics, Department of Psychiatry; University of California, San Diego; La Jolla, California, USA 67University of California, Irvine, Department of Psychiatry and Human Behavior, Irvine, California, USA 68Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark 69Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark 70Center for GeoGenetics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark 71The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark. 72Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands 73Karolinska Institute, Sweden 74Univeristy of North Carolina Hospitals, North Carolina, USA

Collections

Ashkenazi Jewish schizophrenia study

David C. Glahn, Ann E. Pulver

Danish iPSYCH initiative

Anders D. Børglum, Jonas Bybjerg-Grauholm, Jakob Grove, David M. Hougaard, Francesco Lescai, Preben Bo Mortensen, Merete Nordentoft, Thomas M. Werge

McLean psychosis study

Bruce M. Cohen, Mei-Hua Hall, Steven A. McCarroll, Dost Ongur

Pritzker Neuropsychiatric Disorders Research Consortium (Pritzker NDRC)

Huda Akil, Jack D. Barchas, William E. Bunney, William F. Byerley, Lynn DeLisi, Francis S. Lee, Richard M. Myers, Brandi Rollins, Alan Schatzberg, Marquis P. Vawter, Stanley J. Watson

Swedish schizophrenia study

Christina M. Hultman, Jordan W. Smoller, Patrick F. Sullivan

Taiwanese trios study

Wei J. Chen, Stephen V. Faraone, Stephen J. Glatt, Hai-Gwo Hwu, Ming T. Tsuang

UK and Ireland schizophrenia collections

Mariam Al Eissa, Nicholas Bass, Douglas H Blackwood, Gerome Breen, Aiden P. Corvin, Nicholas Craddock, Charles Curtis, David Curtis, Alessia Fiorentino, George Kirov, Andrew McQuillin, Derek W. Morris, Niamh L. O'Brien, Michael C. O'Donovan, Willem H. Ouwehand, Michael J. Owen, Aarno Palotie, Digby Quested, Sally I. Sharp, David St. Clair, James T. Walters

Whole Genome Sequencing in Psychiatric Disorders (WGSPD) consortium and the Genomic Psychiatry Cohort (GPC)

Tim B. Bigdeli, Michael Boehnke, Evelyn J. Bromet, Peter F. Buckley, Michael A. Escamilla, Saana Eskelinen, Tõnu Esko, Ayman H. Fanous, Nelson B. Freimer, Sarah A. Gagliano Taliun, Andrea Ganna, Eija Hämäläinen, Matti Holi, René S. Kahn, Hyun Min Kang, James A. Knowles, Douglas S. Lehrer, Dolores Malaspina, Stephen R. Marder, Helena Medeiros, Lili Milani, Christopher P. Morley, Roel A. Ophoff, Carlos N. Pato, Michele T. Pato, Tiina Paunio, Mark H. Rapaport, Laura J. Scott, Janet l. Sobell, Jaana Suvisaari

Acknowledgements

We would like to thank the patients and families who participated in our studies in the past two decades, without whom our research and findings would not be possible. Research reported in this publication was supported by the National Institute of Mental Health, and the National Human Genome Research Institute of the National Institutes of Health under award numbers: U01MH10564, U01MH105578, R01MH085548 and U54HG003067.

We would also like to acknowledge the generous support from the Stanley Family Foundation, the Kent and Elizabeth Dauten Foundation, and the Dalio Foundation who have enabled us to rapidly expand our data generation collections with the goal of moving towards better treatments for schizophrenia and other psychiatric disorders.