Analysis of Shared Heritability in Common Disorders of the Brain
Publication Date
6-22-2018
Document Type
Article
Organizational Units
College of Arts Humanities and Social Sciences, Psychology
Keywords
Brain disorders, Genetic sharing, Psychiatric disorders, Common genetic variation, Etiology
Abstract
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
Copyright Date
6-22-2018
Copyright Statement / License for Reuse
All Rights Reserved.
Rights Holder
Verneri Anttila, Brendan Bulik-Sullivan, Hilary K. Finucane, Raymond K. Walters, Jose Bras, Laramie Duncan, Valentina Escott-Price, Guido J. Falcone, Padhraig Gormley, Rainer Malik, Nikolaos A. Patsopoulos, Stephan Ripke, Zhi Wei, Dongmei Yu, Phil H. Lee, Patrick Turley, Benjamin Grenier-Boley, Vincent Chouraki, Yoichiro Kamatani, Claudine Berr, Luc Letenneur, Didier Hannequin, Philippe Amouyel, Anne Boland, Jean-François Deleuze, Emmanuelle Duron, Badri N. Vardarajan, Christiane Reitz, Alison M. Goate, Matthew J. Huentelman, M. Ilyas Kamboh, Eric B. Larson, Ekaterina Rogaeva, Peter St George-Hyslop, Hakon Hakonarson, Walter A. Kukull, Lindsay A. Farrer, Lisa L. Barnes, Thomas G. Beach, F. Yesim Demirci, Elizabeth Head, Christine M. Hulette, Gregory A. Jicha, John S.K. Kauwe, Jeffrey A. Kaye, James B. Leverenz, Allan I. Levey, Andrew P. Lieberman, Vernon S. Pankratz, Wayne W. Poon, Joseph F. Quinn, Andrew J. Saykin, Lon S. Schneider, Amanda G. Smith, Joshua A. Sonnen, Robert A. Stern, Vivianna M. Van Deerlin, Linda J. Van Eldik, Denise Harold, Giancarlo Russo, David C. Rubinsztein, Anthony Bayer, Magda Tsolaki, Petra Proitsi, Nick C. Fox, Harald Hampel, Michael J. Owen, Simon Mead, Peter Passmore, Kevin Morgan, Markus M. Nöthen, Jonathan M. Schott, Martin Rossor, Michelle K. Lupton, Per Hoffmann, Johannes Kornhuber, Brian Lawlor, Andrew McQuillin, Ammar Al-Chalabi, Joshua C. Bis, Agustin Ruiz, Mercè Boada, Sudha Seshadri, Alexa Beiser, Kenneth Rice, Sven J. van der Lee, Philip L. De Jager, Daniel H. Geschwind, Matthias Riemenschneider, Steffi Riedel-Heller, Jerome I. Rotter, Gerhard Ransmayr, Bradley T. Hyman, Carlos Cruchaga, Montserrat Alegret, Bendik Winsvold, Priit Palta, Kai-How Farh, Ester Cuenca-Leon, Nicholas Furlotte, Tobias Kurth, Lannie Ligthart, Gisela M. Terwindt, Tobias Freilinger, Caroline Ran, Scott D. Gordon, Guntram Borck, Hieab H.H. Adams, Terho Lehtimäki, Juho Wedenoja, Julie E. 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Weiss, Elena Bacchelli, Anthony Bailey, Vanessa Bal, Agatino Battaglia, Catalina Betancur, Patrick Bolton, Rita Cantor, Patrícia Celestino-Soper, Geraldine Dawson, Silvia De Rubeis, Frederico Duque, Andrew Green, Sabine M. Klauck, Marion Leboyer, Pat Levitt, Elena Maestrini, Shrikant Mane, Daniel Moreno- De-Luca, Jeremy Parr, Regina Regan, Abraham Reichenberg, Sven Sandin, Jacob Vorstman, Thomas Wassink, Ellen Wijsman, Edwin Cook, Susan Santangelo, Richard Delorme, Bernadette Rogé, Tiago Magalhaes, Dan Arking, Thomas G. Schulze, Robert C. Thompson, Jana Strohmaier, Keith Matthews, Ingrid Melle, Derek Morris, Douglas Blackwood, Andrew McIntosh, Sarah E. Bergen, Martin Schalling, Stéphane Jamain, Anna Maaser, Sascha B. Fischer, Céline S. Reinbold, Janice M. Fullerton, Maria Grigoroiu-Serbanescu, José Guzman-Parra, Fermin Mayoral, Peter R. Schofield, Sven Cichon, Thomas W. Mühleisen, Franziska Degenhardt, Johannes Schumacher, Michael Bauer, Philip B. Mitchell, Elliot S. 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Derks, Andrea Dietrich, Thomas Fernandez, Martijn Figee, Nelson Freimer, Gloria Gerber, Marco Grados, Erica Greenberg, Gregory L. Hanna, Andreas Hartmann, Matthew E. Hirschtritt, Pieter J. Hoekstra, Alden Huang, Chaim Huyser, Cornelia Illmann, Michael Jenike, Samuel Kuperman, Bennett Leventhal, Christine Lochner, Gholson J. Lyon, Fabio Macciardi, Marcos Madruga-Garrido, Irene A. Malaty, Athanasios Maras, Lauren M. McGrath , Eurípedes C. Miguel, Pablo Mir, Gerald Nestadt, Humberto Nicolini, Michael S. Okun, Andrew Pakstis, Peristera Paschou, John Piacentini, Christopher Pittenger, Kerstin Plessen, Vasily Ramensky, Eliana M. Ramos, Victor Reus, Margaret A. Richter, Mark A. Riddle, Mary M. Robertson, Veit Roessner, Maria Rosário, Jack F. Samuels, Paul Sandor, Dan J. Stein, Fotis Tsetsos, Filip Van Nieuwerburgh, Sarah Weatherall, Jens R. Wendland, Tomasz Wolanczyk, Yulia Worbe, Gwyneth Zai, Fernando S. Goes, Nicole McLaughlin, Paul S. 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Gejman, Frans Henskens, Morten Mattingsdal, Sang-Yun Oh, Rodney Scott, Bradley Webb, Gerome Breen, Claire Churchhouse, Cynthia M. Bulik, Mark Daly, Martin Dichgans, Stephen V. Faraone, Rita Guerreiro, Peter Holmans, Kenneth S. Kendler, Bobby Koeleman, Carol A. Mathews, Alkes Price, Jeremiah Scharf, Pamela Sklar, Julie Williams, Nicholas W. Wood, Chris Cotsapas, Aarno Palotie, Jordan W. Smoller, Patrick Sullivan, Jonathan Rosand, Aiden Corvin, and Benjamin M. Neale
Provenance
Received from CHORUS
Language
English (eng)
Publication Statement
Copyright is held by the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. User is responsible for all copyright compliance. This article was originally published as:
Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., ..., & Neale, B. M. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395), eaap8757. https://doi.org/10.1126/science.aap8757
Accepted Manuscript is openly available through the "Link to Full Text" button.
The published Version of Record is available at libraries through Compass or Worldcat.
Publication Title
Science
Volume
360
Issue
6395
First Page
eaap8757
ISSN
1095-9203
PubMed ID
29930110
Recommended Citation
Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., ..., & Neale, B. M. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395), eaap8757. https://doi.org/10.1126/science.aap8757