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.
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
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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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William Rayner, Cathryn M. Lewis, Monica Gratacos, Filip Rybakowski, Anna Keski-Rahkonen, Anu Raevuori, James I. Hudson, Ted Reichborn-Kjennerud, Palmiero Monteleone, Andreas Karwautz, Katrin Mannik, Jessica H. Baker, Julie K. O’Toole, Sara E. Trace, Oliver S. P. Davis, Sietske G. Helder, Stefan Ehrlich, Beate Herpertz-Dahlmann, Unna N. Danner, Annemarie A. van Elburg, Maurizio Clementi, Monica Forzan, Elisa Docampo, Jolanta Lissowska, Joanna Hauser, Alfonso Tortorella, Mario Maj, Fragiskos Gonidakis, Konstantinos Tziouvas, Hana Papezova, Zeynep Yilmaz, Gudrun Wagner, Sarah Cohen-Woods, Stefan Herms, Antonio Julià, Raquel Rabionet, Danielle M. Dick, Samuli Ripatti, Ole A. Andreassen, Thomas Espeseth, Astri J. Lundervold, Vidar M. Steen, Dalila Pinto, Stephen W. Scherer, Harald Aschauer, Alexandra Schosser, Lars Alfredsson, Leonid Padyukov, Katherine A. Halmi, James Mitchell, Michael Strober, Andrew W. Bergen, Walter Kaye, Jin Peng Szatkiewicz, Bru Cormand, Josep Antoni Ramos-Quiroga, Cristina Sánchez-Mora, Marta Ribasés, Miguel Casas, Amaia Hervas, Maria Jesús Arranz, Jan Haavik, Tetyana Zayats, Stefan Johansson, Nigel Williams, Josephine Elia, Astrid Dempfle, Aribert Rothenberger, Jonna Kuntsi, Robert D. Oades, Tobias Banaschewski, Barbara Franke, Jan K. Buitelaar, Alejandro Arias Vasquez, Alysa E. Doyle, Andreas Reif, Klaus-Peter Lesch, Christine Freitag, Olga Rivero, Haukur Palmason, Marcel Romanos, Kate Langley, Marcella Rietschel, Stephanie H. Witt, Soeren Dalsgaard, Anders D. Børglum, Irwin Waldman, Beth Wilmot, Nikolas Molly, Claiton H.D. Bau, Jennifer Crosbie, Russell Schachar, Sandra K. Loo, James J. McGough, Eugenio H. Grevet, Sarah E. Medland, Elise Robinson, Lauren A. 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. Gershon, John Rice, James B. Potash, Peter P. Zandi, Nick Craddock, I. Nicol Ferrier, Martin Alda, Guy A. Rouleau, Gustavo Turecki, Roel Ophoff, Carlos Pato, Adebayo Anjorin, Eli Stahl, Markus Leber, Piotr M. Czerski, Howard J. Edenberg, Cristiana Cruceanu, Ian R. Jones, Danielle Posthuma, Till F.M. Andlauer, Andreas J. Forstner, Fabian Streit, Bernhard T. Baune, Tracy Air, Grant Sinnamon, Naomi R. Wray, Donald J. MacIntyre, David Porteous, Georg Homuth, Margarita Rivera, Jakob Grove, Christel M. Middeldorp, Ian Hickie, Michele Pergadia, Divya Mehta, Johannes H. Smit, Rick Jansen, Eco de Geus, Erin Dunn, Qingqin S. Li, Matthias Nauck, Robert A. Schoevers, Aartjan TF Beekman, James A. Knowles, Alexander Viktorin, Paul Arnold, Cathy L. Barr, Gabriel Bedoya-Berrio, O. Joseph Bienvenu, Helena Brentani, Christie Burton, Beatriz Camarena, Carolina Cappi, Danielle Cath, Maria Cavallini, Daniele Cusi, Sabrina Darrow, Damiaan Denys, Eske M. 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. Nestadt, Hans-Jorgen Grabe, Christel Depienne, Anuar Konkashbaev, Nuria Lanzagorta, Ana Valencia-Duarte, Elvira Bramon, Nancy Buccola, Wiepke Cahn, Murray Cairns, Siow A. Chong, David Cohen, Benedicto Crespo-Facorro, James Crowley, Michael Davidson, Lynn DeLisi, Timothy Dinan, Gary Donohoe, Elodie Drapeau, Jubao Duan, Lieuwe Haan, David Hougaard, Sena Karachanak-Yankova, Andrey Khrunin, Janis Klovins, Vaidutis Kučinskas, Jimmy Lee Chee Keong, Svetlana Limborska, Carmel Loughland, Jouko Lönnqvist, Brion Maher, Manuel Mattheisen, Colm McDonald, Kieran C. Murphy, Robin Murray, Igor Nenadic, Jim van Os, Christos Pantelis, Michele Pato, Tracey Petryshen, Digby Quested, Panos Roussos, Alan R. Sanders, Ulrich Schall, Sibylle G. Schwab, Kang Sim, Hon-Cheong So, Elisabeth Stögmann, Mythily Subramaniam, Draga Toncheva, John Waddington, James Walters, Mark Weiser, Wei Cheng, Robert Cloninger, David Curtis, Pablo V. 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 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