Analysis of shared heritability in common disorders of the brain

作者：Verneri Anttila, Brendan K Bulik-Sullivan, Hilary K. Finucane, Raymond Kenney 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 K. Turley, Benjamin Grenier‐Boley, Vincent Antoine Chouraki, Yoichiro Kamatani, Claudine Berr, Luc Letenneur, Didier Hannequin, Philippe Amouyel, Anne Boland, Jean‐François Deleuze, Emmanuelle Duron, Badri Narayan Vardarajan, Christiane Reitz, Alison Goate, Matthew J. Huentelman, M. Ilyas Kamboh, Eric B. Larson, Ekaterina A. Rogaeva, Peter St George‐Hyslop, Hakon H. Hakonarson, Walter A. Kukull, Lindsay A. Farrer, Lisa L. Barnes, Thomas G. Beach, F. Yesim Demirci, Elizabeth Head, Christine Marie 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. S. Poon, Joseph F. Quinn, Andrew J. Saykin, Lon S. S. Schneider, Amanda Smith, Joshua Aaron Sonnen, Robert A. Stern, Vivianna M. Van Deerlin, Linda J. Van Eldik, Denise H. Harold, Giancarlo Russo, David Chaim Rubinsztein, Anthony Bayer, Magda Tsolaki, Petra Proitsi, Nick C. Fox, Harald Juergen Hampel, Michael J. Owen, Simon Mead, Peter Passmore, Kevin Morgan, Markus Maria 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 S. Seshadri, Alexa S. Beiser, Kenneth M. Rice, Sven J. van der Lee, Philip L. De Jager, Daniel H. Geschwind, Matthias Riemenschneider, Steffi Gerlinde Riedel-Heller, Jerome I. Rotter, Gerhard N. Ransmayr, Bradley T. Hyman, Carlos Cruchaga, Montserrat Alegret, Bendik Slagsvold Winsvold, Priit Palta, Kai-How Farh, Ester Cuenca-León, Nicholas A. Furlotte, Tobias Kurth, Lannie Ligthart, Gisela Marie Terwindt, Tobias M. Freilinger, Caroline Ran, Scott D. Gordon, Guntram Borck, Hieab H.H. Adams, Terho J. Lehtimäki, Juho Wedenoja, Julie E. Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Jouke‐Jan Hottenga, Brenda W.J.H. Penninx, Ville Artto, Mari Anneli 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 V Salomaa, Elizabeth A. Loehrer, Hartmut Göbel, Alfons Macaya, Patricia Pozo‐Rosich, Thomas Folkmann Hansen, Thomas Werge, Jaakko A. Kaprio, Andres Metspalu, Christian Kubisch, Michel D. Ferrari, Andrea Carmine Belin, Arn M. J. M. van den Maagdenberg, John‐Anker Zwart, Dorret Irene Boomsma, Nicholas Eriksson, Jes Olesen, Daniel I. Chasman, Dale R. Nyholt, Richard Anney, Andreja Avberšek, Larry Baum, Samuel Frank 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 K. Kälviäinen, Wolfram S. Kunz, Holger Lerche, Costin Leu, Dick Lindhout, Warren David Lo, Daniel H. Lowenstein, Mark McCormack, Rikke Steensbjerre Møller, Anne M. Molloy, Ping-Wing Ng, Karen L. Oliver, Michael Privitera, Rodney A. Radtke, Ann‐Kathrin Ruppert, Thomas H. Sander, Steven C. Schachter, Christoph Josef Schankin, Ingrid Eileen Scheffer, Susanne Schoch, Sanjay M. Sisodiya, Phil E M Smith, Michael R. Sperling, Pasquale Striano, Rainer Surges, G. Neil Thomas, Frank E. Visscher, Christopher D. Whelan, Federico Zara, Erin L. Heinzen, Anthony Guy Marson, Felicitas Becker, Hans Stroink, Fritz Zimprich, Thomas Gasser, J. Raphael Gibbs, Peter Heutink, María Martínez, Huw R. Morris, Manu Sharma, Mina Ryten, Kin Ying Mok, Sara L. Pulit, Steve Bevan, Elizabeth Holliday, John Attia, Thomas W.K. Battey, Giorgio Battista Boncoraglio, Vincent Thijs, Wei‐Min Chen, Braxton D. Mitchell, Peter Malcolm Rothwell, Pankaj Kumar Sharma, Cathie L. M. Sudlow, Astrid Moura Vicente, Hugh S. Markus, Christina E. Kourkoulis, Joanna Pera, Miriam R. Raffeld, Scott L. 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 F. K. 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 Nora Danner, Annemarie Elburg, Maurizio Clementi, Monica Forzan, Elisa Docampo, Jolanta Lissowska, Joanna D. Hauser, Alfonso Antonio Vincenzo Tortorella, Mario Maj, Fragiskos K. Gonidakis, Konstantinos Tziouvas, Hana Papežová, Zeynep Yamancan Yılmaz, Gudrun Wagner, Sarah Cohen‐Woods, Stefan Herms, Antonio Julià, Raquel Rabionet, Danielle M. Dick, Samuli Ripatti, Ole A. Andreassen, Thomas Espeseth, Astri Johansen Lundervold, Vidar Martin Steen, Dalila Pinto, Stephen W. Scherer, Harald N. Aschauer, Alexandra Schosser, Lars S. Alfredsson, Leonid Padyukov, Katherine Ann Halmi, James Earl Mitchell, Michael A. Strober, Andrew W. Bergen, Walter H. Kaye, Jin Peng Szatkiewicz, Bru Cormand, Josep Antoni Ramos‐Quiroga, Cristina Sánchez‐Mora, Marta Ribasés, Miguel Casas, Amaia Hervás, Maria Jesús Arranz, Jan Haavik, Tetyana Zayats, Stefan E. Johansson, Nigel M. 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 Margarete Freitag, Olga Rivero, Haukur Pálmason, Marcel Romanos, K. Langley, Marcella Rietschel, Stephanie H. Witt, Soeren Dalsgaard, Anders Dupont Børglum, Irwin D. Waldman, Beth Wilmot, Molly A. Nikolas, Claiton H.D. Bau, Jennifer Crosbie, Russell James Schachar, Sandra K. Loo, James J. McGough, Eugenio Horácio Grevet, Sarah Elizabeth Medland, Elise Robinson, Lauren A. Weiss, Elena Bacchelli, Anthony J. Bailey, Vanessa Hus 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 R Parr, Regina Regan, Abraham Reichenberg, Sven Sandin, Jacob A. S. 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, Keith Matthews, Ingrid S. Melle, Derek W. Morris, Douglas Blackwood, Andrew Mark McIntosh, Sarah E. Bergen, Martin Schalling, Stéphane Jamain, Anna Maaser, Sascha B. Fischer, Céline Sonja Reinbold, Janice M. Fullerton, Maria Grigoroiu‐Serbânescu, Jose Guzman Parra, Fermín Mayoral, Peter R. Schofield, Sven Cichon, Thomas W. Mühleisen, Franziska Degenhardt, Johannes Schumacher, Michael Bauer, Philip Bowden Mitchell, Elliot S. Gershon, John Rice, James B. Potash, Peter P. Zandi, Nick J. Craddock, I. Nicol Ferrier, Martin Alda, Guy Armand Rouleau, Gustavo Turecki, Roel A. Ophoff, Carlos N. Pato, Adebayo Anjorin, Eli Stahl, Markus Leber, Piotr M. Czerski, Howard J. Edenberg, Cristiana Cruceanu, Ian Richard 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 Maria Middeldorp, Ian Bernard Hickie, Michele L. Pergadia, Divya Mehta, Johannes H. Smit, Rick Jansen, Eco J. C. de Geus, Erin Dunn, Qingqin S. Li, Matthias A. Nauck, Robert A. Schoevers, Aartjan T.F. Beekman, James A. Knowles, Alexander Viktorin, Paul D. Arnold, Cathy L. Barr, Gabriel de Jesús Bedoya-Berrío, Oscar Joseph Bienvenu, Helena Brentani, Christie L. Burton, Beatríz Camarena, Carolina Cappi, Daniëlle C. Cath, Maria Cristina Cavallini, Daniele Cusi, Sabrina Michelle Darrow, Damiaan A J P Denys, Eske M. Derks, Andrea Dietrich, Thomas V. Fernandez, Martijn Figee, Nelson B. Freimer, Gloria Frances 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 L. LEVENTHAL, Christine Löchner, Gholson J. Lyon, Fabio M. Macciardi, Marcos Madruga-Garrido, Irene A. Malaty, Athanasios Maras, Lauren M. McGrath, Eurı́pedes Constantino Miguel, Pablo Mir, Gerald Nestadt, Humberto Nicolini, Michael S. Okun, ANDREW J. PAKSTIS, Peristera Paschou, John C. Piacentini, Christopher Pittenger, Kerstin Jessica Plessen, Vasily E. Ramensky, Eliana Marisa Ramos, Victor I. Reus, Margaret Anne Richter, Mark A. Riddle, Mary May Robertson, Veit Roessner, Maria Conceição do Rosário, JACK F. SAMUELS, Paul Sandor, Dan J. Stein, Fotis Tsetsos, Filip Van Nieuwerburgh, Sarah L. Weatherall, Jens R. Wendland, Tomasz Wolańczyk, Yulia Worbe, Gwyneth C. Zai, Fernando S. Goes, Nicole C R McLaughlin, Paul Sasha Nestadt, Hans Jörgen Grabe, Christel Depienne, Anuar I. 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 H Davidson, Lynn E. DeLisi, Timothy G. Dinan, Gary J Donohoe, Elodie Drapeau, Jubao Duan, Lieuwe de Haan, DAVID MICHAEL HOUGAARD, Sena Karachanak-Yankova, Andrey Khrunin, Jānis Kloviņš, Vaidutis Kučinskas, Jimmy Lee, Svetlana Limborska, Carmel Maree Loughland, Jouko K Lönnqvist, Brion S. Maher, Manuel Mattheisen, Colm McDonald, Kieran C. Murphy, Robin M. Murray, Igor Nenadić, Jim van Os, Christos Pantelis, Michele T. Pato, Tracey L. Petryshen, Digby J. Quested, Panos Roussos, Alan R. Sanders, Ulrich Schall, Sibylle G. Schwab, Kang Sim, Hon‐Cheong So, Elisabeth Stögmann, Mythily Subramaniam, Draga Ivanova Toncheva, John L. Waddington, James Walters, Mark Weiser, Wei Cheng, Robert C. Cloninger, David Curtis, Pablo V. Gejman, Frans A. Henskens, Morten Mattingsdal, Sang-Yun Oh, Rodney J. Scott, Bradley Todd Webb, Gerome D. Breen, Claire Churchhouse, Cynthia Marie Bulik, Mark J. Daly, Martin Dichgans, Stephen V. Faraone, Rita João Guerreiro, Peter Holmans, Kenneth S. Kendler, Bobby P.C. Koeleman, Carol A. Mathews, Alkes L. Price, Jeremiah M. Scharf, Pamela B. Sklar, Julie H. Williams, Nicholas Wood, Chris J. Cotsapas, Aarno V. Palotie, Jordan W. Smoller, Patrick F. Sullivan, Jonathan M. Rosand, Aiden P. Corvin, Benjamin M. Neale · 发表于：Science · 年份：2018 · DOI：10.1126/science.aap8757 · 被引用次数：2056 · 研究领域：Genetic Associations and Epidemiology、Genomics and Rare Diseases、Autism Spectrum Disorder Research

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.