Analysis of shared heritability in common disorders of the brain

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 BerrLuc 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. 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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 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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571 Citations (Scopus)

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.

Original languageEnglish
Article numbereaap8757
JournalScience
Volume360
Issue number6395
Number of pages40
ISSN0036-8075
DOIs
Publication statusPublished - 22 Jun 2018

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