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Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

  • S. Hong Lee
  • , Stephan Ripke
  • , Benjamin M. Neale
  • , Stephen V. Faraone
  • , Shaun M. Purcell
  • , Roy H. Perlis
  • , Bryan J. Mowry
  • , Anita Thapar
  • , Michael E. Goddard
  • , John S. Witte
  • , Devin Absher
  • , Ingrid Agartz
  • , Huda Akil
  • , Farooq Amin
  • , Ole A. Andreassen
  • , Adebayo Anjorin
  • , Richard Anney
  • , Verneri Anttila
  • , Dan E. Arking
  • , Philip Asherson
  • Maria H. Azevedo, Lena Backlund, Judith A. Badner, Anthony J. Bailey, Tobias Banaschewski, Jack D. Barchas, Michael R. Barnes, Thomas B. Barrett, Nicholas Bass, Agatino Battaglia, Michael Bauer, Mònica Bayés, Frank Bellivier, Sarah E. Bergen, Wade Berrettini, Catalina Betancur, Thomas Bettecken, Joseph Biederman, Elisabeth B. Binder, Donald W. Black, Douglas H.R. Blackwood, Cinnamon S. Bloss, Michael Boehnke, Dorret I. Boomsma, Gerome Breen, René Breuer, Richard Bruggeman, Paul Cormican, Nancy G. Buccola, Jan K. Buitelaar, William E. Bunney, Joseph D. Buxbaum, William F. Byerley, Enda M. Byrne, Sian Caesar, Wiepke Cahn, Rita M. Cantor, Miguel Casas, Aravinda Chakravarti, Kimberly Chambert, Khalid Choudhury, Sven Cichon, C. Robert Cloninger, David A. Collier, Edwin H. Cook, Hilary Coon, Bru Cormand, Aiden Corvin, William H. Coryell, David W. Craig, Ian W. Craig, Jennifer Crosbie, Michael L. Cuccaro, David Curtis, Darina Czamara, Susmita Datta, Geraldine Dawson, Richard Day, Eco J. De Geus, Franziska Degenhardt, Srdjan Djurovic, Gary J. Donohoe, Alysa E. Doyle, Jubao Duan, Frank Dudbridge, Eftichia Duketis, Richard P. Ebstein, Howard J. Edenberg, Josephine Elia, Sean Ennis, Bruno Etain, Ayman Fanous, Anne E. Farmer, I. Nicol Ferrier, Matthew Flickinger, Eric Fombonne, Tatiana Foroud, Josef Frank, Barbara Franke, Christine Fraser, Robert Freedman, Nelson B. Freimer, Christine M. Freitag, Marion Friedl, Louise Frisén, Louise Gallagher, Pablo V. Gejman, Lyudmila Georgieva, Elliot S. Gershon, Daniel H. Geschwind, Ina Giegling, Michael Gill, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Tiffany A. Greenwood, Dorothy E. Grice, Magdalena Gross, Detelina Grozeva, Weihua Guan, Hugh Gurling, Lieuwe De Haan, Jonathan L. Haines, Hakon Hakonarson, Joachim Hallmayer, Steven P. Hamilton, Marian L. Hamshere, Thomas F. Hansen, Annette M. Hartmann, Martin Hautzinger, Andrew C. Heath, Anjali K. Henders, Stefan Herms, Ian B. Hickie, Maria Hipolito, Susanne Hoefels, Peter A. Holmans, Florian Holsboer, Witte J. Hoogendijk, Jouke Jan Hottenga, Christina M. Hultman, Vanessa Hus, Andrés Ingason, Marcus Ising, Stéphane Jamain, Edward G. Jones, Ian Jones, Lisa Jones, Jung Ying Tzeng, Anna K. Kähler, René S. Kahn, Radhika Kandaswamy, Matthew C. Keller, James L. Kennedy, Elaine Kenny, Lindsey Kent, Yunjung Kim, George K. Kirov, Sabine M. Klauck, Lambertus Klei, James A. Knowles, Martin A. Kohli, Daniel L. Koller, Bettina Konte, Ania Korszun, Lydia Krabbendam, Robert Krasucki, Jonna Kuntsi, Phoenix Kwan, Mikael Landén, Niklas Långström, Mark Lathrop, Jacob Lawrence, William B. Lawson, Marion Leboyer, David H. Ledbetter, Phil H. Lee, Todd Lencz, Klaus Peter Lesch, Douglas F. Levinson, Cathryn M. Lewis, Jun Li, Paul Lichtenstein, Jeffrey A. Lieberman, Dan Yu Lin, Don H. Linszen, Chunyu Liu, Falk W. Lohoff, Sandra K. Loo, Catherine Lord, Jennifer K. Lowe, Susanne Lucae, Donald J. Macintyre, Pamela A.F. Madden, Elena Maestrini, Patrik K.E. Magnusson, Pamela B. Mahon, Wolfgang Maier, Anil K. Malhotra, Shrikant M. Mane, Christa L. Martin, Nicholas G. Martin, Manuel Mattheisen, Keith Matthews, Morten Mattingsdal, Steven A. Mccarroll, Kevin A. Mcghee, James J. Mcgough, Patrick J. Mcgrath, Peter Mcguffin, Melvin G. Mcinnis, Andrew Mcintosh, Rebecca Mckinney, Alan W. Mclean, Francis J. Mcmahon, William M. Mcmahon, Andrew Mcquillin, Helena Medeiros, Sarah E. Medland, Sandra Meier, Ingrid Melle, Fan Meng, Jobst Meyer, Christel M. Middeldorp, Lefkos Middleton, Vihra Milanova, Ana Miranda, Anthony P. Monaco, Grant W. Montgomery, Jennifer L. Moran, Daniel Moreno-De-Luca, Gunnar Morken, Derek W. Morris, Eric M. Morrow, Valentina Moskvina, Pierandrea Muglia, Thomas W. Mühleisen, Walter J. Muir, Bertram Müller-Myhsok, Michael Murtha, Richard M. Myers, Inez Myin-Germeys, Michael C. Neale, Stan F. Nelson, Caroline M. Nievergelt, Ivan Nikolov, Vishwajit Nimgaonkar, Willem A. Nolen, Markus M. Nöthen, John I. Nurnberger, Evaristus A. Nwulia, Dale R. Nyholt, Colm O'dushlaine, Robert D. Oades, Ann Olincy, Guiomar Oliveira, Line Olsen, Roel A. Ophoff, Urban Osby, Michael J. Owen, Aarno Palotie, Jeremy R. Parr, Andrew D. Paterson, Carlos N. Pato, Michele T. Pato, Brenda W. Penninx, Michele L. Pergadia, Margaret A. Pericak-Vance, Benjamin S. Pickard, Jonathan Pimm, Joseph Piven, Danielle Posthuma, James B. Potash, Fritz Poustka, Peter Propping, Vinay Puri, Digby J. Quested, Emma M. Quinn, Josep Antoni Ramos-Quiroga, Henrik B. Rasmussen, Soumya Raychaudhuri, Karola Rehnström, Andreas Reif, Marta Ribasés, John P. Rice, Marcella Rietschel, Kathryn Roeder, Herbert Roeyers, Lizzy Rossin, Aribert Rothenberger, Guy Rouleau, Douglas Ruderfer, Dan Rujescu, Alan R. Sanders, Stephan J. Sanders, Susan L. Santangelo, Joseph A. Sergeant, Russell Schachar, Martin Schalling, Alan F. Schatzberg, William A. Scheftner, Gerard D. Schellenberg, Stephen W. Scherer, Nicholas J. Schork, Thomas G. Schulze, Johannes Schumacher, Markus Schwarz, Edward Scolnick, Laura J. Scott, Jianxin Shi, Paul D. Shilling, Stanley I. Shyn, Jeremy M. Silverman, Susan L. Slager, Susan L. Smalley, Johannes H. Smit, Erin N. Smith, Edmund J.S. Sonuga-Barke, David St. Clair, Matthew State, Michael Steffens, Hans Christoph Steinhausen, John S. Strauss, Jana Strohmaier, T. Scott Stroup, James S. Sutcliffe, Peter Szatmari, Szabocls Szelinger, Srinivasa Thirumalai, Robert C. Thompson, Alexandre A. Todorov, Federica Tozzi, Jens Treutlein, Manfred Uhr, Edwin J.C.G. Van Den Oord, Gerard Van Grootheest, Jim Van Os, Astrid M. Vicente, Veronica J. Vieland, John B. Vincent, Peter M. Visscher, Christopher A. Walsh, Thomas H. Wassink, Stanley J. Watson, Myrna M. Weissman, Thomas Werge, Thomas F. Wienker, Ellen M. Wijsman, Gonneke Willemsen, Nigel Williams, A. Jeremy Willsey, Stephanie H. Witt, Wei Xu, Allan H. Young, Timothy W. Yu, Stanley Zammit, Peter P. Zandi, Peng Zhang, Frans G. Zitman, Sebastian Zöllner, Bernie Devlin, John R. Kelsoe, Pamela Sklar, Mark J. Daly, Michael C. O'donovan, Nicholas Craddock, Patrick F. Sullivan, Jordan W. Smoller, Kenneth S. Kendler, Naomi R. Wray*
*Corresponding author for this work
  • University of Queensland
  • Massachusetts General Hospital
  • Broad Institute
  • SUNY Upstate Medical University
  • Icahn School of Medicine at Mount Sinai
  • Queensland Centre for Mental Health Research
  • Cardiff University
  • Biosciences Research Division
  • University of Melbourne
  • University of California at San Francisco
  • HudsonAlpha Institute for Biotechnology
  • University of Oslo
  • Diakonhjemmet Hospital
  • University of Michigan, Ann Arbor
  • Emory University
  • University College London
  • Trinity College Dublin
  • Johns Hopkins University
  • King's College London
  • University of Coimbra
  • Karolinska Institutet
  • The University of Chicago
  • University of British Columbia
  • Heidelberg University 
  • Cornell University
  • GlaxoSmithKline
  • Portland VA Medical Center
  • IRCCS Fondazione Stella Maris - Calambrone (Pisa)
  • Technische Universität Dresden
  • University of Barcelona
  • Institut national de la santé et de la recherche médicale
  • Université Paris Cité
  • Assistance publique – Hôpitaux de Paris
  • Fondation FondaMental
  • University of Pennsylvania
  • CNRS
  • Sorbonne Université
  • Max Planck Institute of Psychiatry
  • University of Iowa
  • University of Edinburgh
  • Scripps Research Translational Institute
  • Scripps Health
  • Vrije Universiteit Amsterdam
  • NIHR Maudsley Biomedical Research Centre
  • University of Groningen
  • Louisiana State University Health Sciences Center
  • Radboud University Nijmegen
  • University of California at Irvine
  • NCIRE (Northern California Institute of Q Research and Education)
  • University of Birmingham
  • Utrecht University
  • University of California at Los Angeles
  • University Hospital Vall d'Hebron
  • Autonomous University of Barcelona
  • University of Bonn
  • Jülich Research Centre
  • University of Basel
  • Washington University St. Louis
  • University of Illinois at Chicago
  • University of Utah
  • Centro de Investigación en Red de Enfermedades Raras (CIBERER)
  • Translational Genomics Research Institute
  • University of Toronto
  • University of Miami
  • Queen Mary University of London
  • Munich Cluster for Systems Neurology (SyNergy)
  • Autism Speaks Inc.
  • University of North Carolina at Chapel Hill
  • University of Dundee
  • Vrije Universiteit (VU)
  • NorthShore University HealthSystem
  • London School of Hygiene and Tropical Medicine
  • Goethe University Frankfurt
  • National University of Singapore
  • Indiana University Bloomington
  • University College Dublin
  • Université Paris-Est Créteil
  • Hôpital Henri Mondor
  • Georgetown University
  • Virginia Commonwealth University
  • Newcastle University
  • Oregon Health and Science University
  • University of Colorado Anschutz Medical Campus
  • Martin Luther University Halle-Wittenberg
  • Queensland Institute of Medical Research
  • University of Plymouth
  • University of California at San Diego
  • University of Minnesota Twin Cities
  • University of Amsterdam
  • Vanderbilt University
  • Children's Hospital of Philadelphia
  • Stanford University
  • University of Copenhagen
  • iPSYCH
  • University of Tübingen
  • The University of Sydney
  • Howard University
  • Erasmus University Rotterdam
  • University of California at Davis
  • North Carolina State University
  • University of Colorado Boulder
  • University of St Andrews
  • German Cancer Research Center
  • University of Pittsburgh
  • University of Southern California
  • Maastricht University
  • University of Gothenburg
  • Centre National de Recherche en Génomique Humaine
  • Geisinger Medical Center
  • The Zucker Hillside Hospital
  • Feinstein Institute of Medical Research
  • Albert Einstein College of Medicine
  • University of Würzburg
  • Columbia University
  • Amsterdam University Medical Centers
  • University of Bologna
  • Yale University
  • Aarhus University
  • Sørlandet Hospital
  • National Institutes of Health
  • Trier University
  • Imperial College London
  • Medical University Sofia
  • University of Valencia
  • University of Oxford
  • Tufts University
  • Norwegian University of Science and Technology
  • Brown University
  • University of Duisburg-Essen
  • Wellcome Trust Sanger Institute
  • VU University Medical Center
  • Vall d'Hebron Research Institute
  • Carnegie Mellon University
  • Ghent University
  • University of Göttingen
  • McGill University
  • Maine Medical Center
  • Harvard University
  • Rush University Medical Center
  • Scripps Research Institute
  • Psychiatric Center Nordbaden
  • University of Washington
  • Mayo Clinic Rochester, MN
  • University of Southampton
  • University of Aberdeen
  • Federal Institute for Drugs and Medical Devices (BfArM)
  • Aalborg University
  • University of Zurich
  • Oxford Health NHS Foundation Trust
  • Instituto Nacional de Saúde Doutor Ricardo Jorge
  • University of Lisbon
  • Instituto Gulbenkian de Medicina Molecular
  • Nationwide Children’s Hospital
  • Boston Children's Hospital
  • Leiden University
  • Department of Veterans Affairs

Research output: Contribution to journalArticlepeer-review

Abstract

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Original languageEnglish
Pages (from-to)984-994
Number of pages11
JournalNature Genetics
Volume45
Issue number9
DOIs
Publication statusPublished - Sept 2013
Externally publishedYes

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