Analysis of shared heritability in common disorders of the brain

著者: Verneri Anttila, Brendan Bulik‐Sullivan, Hilary K. Finucane, Raymond K. Walters, José Brás, Laramie E. 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 Goate, Matthew J. Huentelman, M. Ilyas Kamboh, Eric B. Larson, Ekaterina Rogaeva, Peter St George‐Hyslop, Håkon Håkonarson, 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, V. Shane Pankratz, Wayne W. Poon, Joseph F. Quinn, Andrew J. Saykin, Lon S. Schneider, Amanda 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 N. Rossor, Michelle K. Lupton, Per Hoffmann, Johannes Kornhuber, Brian Lawlor, Andrew McQuillin, Ammar Al‐Chalabi, Joshua C Bis, Agustı́n Ruiz, Merçé Boada, Sudha Seshadri, Alexa Beiser, Kenneth Rice, Sven J. van der Lee, Philip L. De Jager, Daniel H. Geschwind, Matthias Riemenschneider, Steffi G. Riedel‐Heller, Jerome I. Rotter, Gerhard Ransmayr, Bradley T. Hyman, Carlos Cruchaga, Montserrat Alegret, Bendik S. Winsvold, Priit Palta, Kai-How Farh, Ester Cuenca-León, Nicholas A. 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. Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Jouke‐Jan Hottenga, Brenda W.J.H. Penninx, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Nicholas G. Martin, Grant W. Montgomery, Mitja Kurki, Eija Hämäläinen, Hailiang Huang, Jie Huang, Cynthia Sandor, Caleb Webber, Bertram Müller‐Myhsok, Stefan Schreiber, Veikko Salomaa, Elizabeth Loehrer, Hartmut Göbel, Alfons Macaya, Patricia Pozo‐Rosich, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Andres Metspalu, Christian Kubisch, Michel D. Ferrari, Andrea Carmine Belin, Arn M. J. M. van den Maagdenberg, John‐Anker Zwart, Dorret I. Boomsma, Nicholas Eriksson, Jes Olesen, Daniel I. Chasman, Dale R. Nyholt, Richard Anney, Andreja Avberšek, Larry Baum, Samuel F. Berkovic, Jonathan P. Bradfield, Russell J. Buono, Claudia B. Catarino, Patrick Cossette, Peter De Jonghe, Chantal Depondt, Dennis Dlugos, Thomas N. Ferraro, Jacqueline A. French, Helle Hjalgrim, Jennifer Jamnadas-Khoda, Reetta Kälviäinen, Wolfram S. Kunz, Holger Lerche, Costin Leu, Dick Lindhout, Warren Lo, Daniel H. Lowenstein, Mark McCormack, Rikke S. Møller, Anne M. Molloy, Ping-Wing Ng, Karen Oliver, Michael Privitera, Rodney A. Radtke, Ann‐Kathrin Ruppert, Thomas Sander, Steven C. Schachter, Christoph J. Schankin, Ingrid E. Scheffer, Susanne Schoch, Sanjay M. Sisodiya, Phil E M Smith, Michael R. Sperling, Pasquale Striano, Rainer Surges, G. Neil Thomas, Frank Visscher, Christopher D. Whelan, Federico Zara, Erin L. Heinzen, Anthony G Marson, Felicitas Becker, Hans Stroink, Fritz Zimprich, Thomas Gasser, J. Raphael Gibbs, Peter Heutink, María Martínez, Huw R. Morris, Manu Sharma, Mina Ryten, Kin Y. Mok, Sara L. Pulit, Steve Bevan, Elizabeth Holliday, John Attia, Thomas W.K. Battey, Giorgio B. Boncoraglio, Vincent Thijs, Wei‐Min Chen, Braxton D. Mitchell, Peter M. Rothwell, Pankaj Sharma, Cathie Sudlow, Astrid M. Vicente, Hugh S. Markus, Christina Kourkoulis, Joanna Pera, Miriam R. Raffeld, Scott Silliman, Vesna Boraska Perica, Laura M. Thornton, Laura M. Huckins, N. William Rayner, Cathryn M. Lewis, Mónica Gratacòs, Filip Rybakowski, Anna Keski‐Rahkonen, Anu Raevuori, James I. Hudson, Ted Reichborn‐Kjennerud, Palmiero Monteleone, Andreas Karwautz, Katrin Männik, 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 Elburg, Maurizio Clementi, Monica Forzan, Elisa Docampo, Jolanta Lissowska, Joanna Hauser, Alfonso Tortorella, Mario Maj, Fragiskos Gonidakis, Konstantinos Tziouvas, Hana Papežová, Zeynep Yılmaz, 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, H.N. Aschauer, Alexandra Schosser, Lars Alfredsson, Leonid Padyukov, Katherine A. Halmi, James E. Mitchell, Michael Strober, Andrew W. Bergen, Walter H. Kaye, Jin P. Szatkiewicz, Bru Cormand, Josep Antoni Ramos‐Quiroga, Cristina Sánchez‐Mora, Marta Ribasés, Miguel Casas, Amaia Hervás, María J. 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 Vásquez, Alysa E. Doyle, Andreas Reif, Klaus‐Peter Lesch, Christine M. Freitag, Olga Rivero, Haukur Pálmason, Marcel Romanos, K. Langley, Marcella Rietschel, Stephanie H. Witt, Soeren Dalsgaard, Anders D. Børglum, Irwin D. Waldman, Beth Wilmot, Molly A. Nikolas, Claiton H.D. Bau, Jennifer Crosbie, Russell Schachar, Sandra K. Loo, James J. McGough, Eugênio H. Grevet, Sarah E. Medland, Elise Robinson, Lauren A. Weiss, Elena Bacchelli, Anthony Bailey, Vanessa H. Bal, Agatino Battaglia, Catalina Betancur, Patrick Bolton, Rita M. Cantor, Patrícia B. S. Celestino-Soper, Géraldine 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 H. Wassink, Ellen M. Wijsman, Edwin H. Cook, Susan L. Santangelo, Richard Delorme, Bernadette Rogé, Tiago R. Magalhães, Dan E. Arking, Thomas G. Schulze, Robert C. Thompson, Jana Strohmaier, K. Matthews, Ingrid Melle, Derek W. Morris, Douglas Blackwood, Andrew M. McIntosh, Sarah E. Bergen, Martin Schalling, Stéphane Jamain, Anna Maaser, Sascha B. Fischer, Céline S. Reinbold, Janice M. Fullerton, Maria Grigoroiu‐Serbânescu, José Guzmán‐Parra, Fermín 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 A. Ophoff, Carlos N. Pato, Adebayo Anjorin, Eli Stahl, Markus Leber, Piotr M. Czerski, Howard J. Edenberg, Cristiana Cruceanu, Ian Jones, Daniëlle Posthuma, Till F. M. Andlauer, Andreas J. Forstner, Fabian Streit, Bernhard T. Baune, Tracy Air, Grant Sinnamon, Naomi R. Wray, Donald J. MacIntyre, David J. Porteous, Georg Homuth, Margarita Rivera, Jakob Grove, Christel M. Middeldorp, Ian B. Hickie, Michele L. Pergadia, Divya Mehta, Johannes H. Smit, Rick Jansen, Eco J. C. de Geus, Erin Dunn, Qingqin S. Li, Matthias Nauck, Robert A. Schoevers, Aartjan T.F. Beekman, James A. Knowles, Alexander Viktorin, Paul D. Arnold, Cathy L. Barr, Gabriel Bedoya‐Berrío, O. Joseph Bienvenu, Helena Brentani, Christie L. Burton, Beatríz Camarena, Carolina Cappi, Daniëlle C. Cath, Maria Cristina Cavallini, Daniele Cusi, Sabrina M. Darrow, Damiaan Denys, Eske M. Derks, Andrea Dietrich, Thomas Fernandez, Martijn Figee, Nelson B. Freimer, Gloria F. Gerber, Marco A. Grados, Erica Greenberg, Gregory L. Hanna, Andreas Hartmann, Matthew E. Hirschtritt, Pieter J. Hoekstra, Alden Huang, Chaim Huyser, Cornelia Illmann, Michael A. Jenike, Samuel Kuperman, Bennett Leventhal, Christine Löchner, Gholson J. Lyon, Fabìo Macciardi, Marcos Madruga-Garrido, Irene A. Malaty, Athanasios Maras, Lauren M. McGrath, Eurı́pedes Constantino Miguel, Pablo Mir, Gerald Nestadt, Humberto Nicolini, Michael S. Okun, A.J. Pakstis, Peristera Paschou, John Piacentini, Christopher Pittenger, Kerstin Jessica Plessen, Vasily Ramensky, Eliana Marisa Ramos, Victor I. Reus, Margaret A. Richter, Mark A. Riddle, Mary M. Robertson, Veit Roessner, Maria Conceição do Rosário, Jack Samuels, Paul Sandor, Dan J. Stein, Fotis Tsetsos, Filip Van Nieuwerburgh, Sarah L. Weatherall, Jens R. Wendland, Tomasz Wolańczyk, Yulia Worbe, Gwyneth Zai, Fernando S. Goes, Nicole McLaughlin, Paul S. Nestadt, Hans J. Grabe, Christel Depienne, Anuar Konkashbaev, Nuria Lanzagorta, Ana Valencia, Elvira Bramon, Nancy G. Buccola, Wiepke Cahn, Murray J. Cairns, Siow Ann Chong, David Cohen, Benedicto Crespo‐Facorro, James J. Crowley, Michael Davidson, Lynn E. DeLisi, Timothy G. Dinan, Gary Donohoe, Elodie Drapeau, Jubao Duan, Lieuwe de Haan, David M. Hougaard, Sena Karachanak-Yankova, Andrey Khrunin, Jānis Kloviņš, Vaidutis Kučinskas, Jimmy Lee, Limborskaia Sa, Carmel M. Loughland, Jouko Lönnqvist, Brion S. Maher, Manuel Mattheisen, Colm McDonald, Kieran C. Murphy, Robin Murray, Igor Nenadić, Jim van Os, Christos Pantelis, Michele T. Pato, Tracey L. Petryshen, Digby Quested, Panos Roussos, Alan R. Sanders, Ulrich Schall, Sibylle G. Schwab, Kang Sim, Hon‐Cheong So, Elisabeth Stögmann, Mythily Subramaniam, Драга Тончева, John L. Waddington, James Walters, Mark Weiser, Wei Cheng, Robert Cloninger, David Curtis, Pablo V. Gejman, Frans A. Henskens, Morten Mattingsdal, Sang-Yun Oh, Rodney J. Scott, Bradley T. Webb, Gerome Breen, Claire Churchhouse, Cynthia M. Bulik, Mark J. Daly, Martin Dichgans, Stephen V. Faraone, Rita Guerreiro, Peter Holmans, Kenneth S. Kendler, Bobby P.C. Koeleman, Carol A. Mathews, Alkes L. Price, Jeremiah M. Scharf, Pamela Sklar, Julie Williams, Nicholas Wood, Chris Cotsapas, Aarno Palotie, Jordan W. Smoller, Patrick F. Sullivan, Jonathan Rosand, Aiden Corvin, Benjamin M. Neale - Science 2018 被引用: 2,050

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.