| Title: |
Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders |
| Authors: |
Lee, Phil H.; Anttila, Verneri; Won, Hyejung; Feng, Yen-Chen; Rosenthal, Jacob; Zhu, Zhaozhong; Tucker-Drob, Elliot M.; Nivard, Michel G.; Grotzinger, Andrew D.; Posthuma, Danielle; Wang, Meg M.-J.; Yu, Dongmei; Stahl, Eli; Walters, Raymond K.; Anney, Richard J.L.; Duncan, Laramie E.; Belangero, Sintia; Luykx, Jurjen; Kranzler, Henry; Keski-Rahkonen, Anna; Cook, Edwin H.; Kirov, George; Kaprio, Giovanni Coppola-Jaakko; Zai, Clement C.; Hoekstra, Pieter J.; Rohde, Tobias Banaschewski-Luis A.; Martin, Joanna; Agerbo, Esben; Baldursson, Gı́sli; Belliveau, Richard; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Cerrato, Felecia; Chambert, Kimberly; Churchhouse, Claire; Jennifer, Crosbie; Dumont, Ashley; Grove, Jakob; Gudmundsson, Olafur O.; Hansen, Christine S.; Howrigan, Daniel P.; Huang, Hailiang; Martin, Alicia R.; Palmer, Duncan S.; Pedersen, Carsten B.; Pedersen, Marianne G.; Poterba, Timothy; Poulsen, Jesper B.; Satterstrom, F. Kyle; Stefansson, Hreinn; Turley, Patrick; Burton, Christie L.; Hakonarson, Hakon; Lesch, Klaus-Peter; Reif, Andreas; Schachar, Russell; Medland, Sarah E.; Hougaard, David M.; Werge, Thomas; Mors, Ole; Mortensen, Preben B.; Bettella, Francesco; Christensen, Jane H.; Rubeis, Silvia De; Djurovic, Srdjan; Hultman, Christina M.; Klei, Lambertus; Nyegaard, Mette; Nærland, Terje; Pourcain, Beate St; Qvist, Per; Rehnström, Karola; Reichenberg, Abraham; Reichert, Jennifer; Roeder, Kathryn; Saemundsen, Evald; Sandin, Sven; Holmans, Peter A.; Weiss, Lauren A.; Delorme, Richard; Grice, Dorothy E.; Ladd-Acosta, Christine; Magnusson, Pall; Pinto, Dalila; Rouleau, Guy A.; Willsey, A. Jeremy; Coon, Hilary; Sutcliffe, James S.; Arking, Dan E.; Stefansson, Kari; Forstner, Andreas J.; McQuillin, Andrew; Wang, Yunpeng; Coleman, Jonathan R. I.; Gaspar, Héléna A.; Byrne, Enda M.; Akil, Huda; Albani, Diego; Anjorin, Adebayo; Bass, Nicholas; Bauer, Michael; Bergen, Sarah E.; Budde, Monika; Bunney, William; Byerley, William; Clarke, Toni-Kim; Curtis, David; Dale, Anders M.; Elvsåshagen, Torbjørn; Fischer, Sascha B.; Forty, Liz; Frank, Josef; Gade, Katrin; Gordon, Scott D.; Gordon-Smith, Katherine; Greenwood, Tiffany A.; Guzman-Parra, José; Hautzinger, Martin; Heilbronner, Urs; Herms, Stefan; Hoffmann, Per; Holland, Dominic; Jamain, Stéphane; Kandaswamy, Radhika; Kennedy, James L.; Kittel-Schneider, Sarah; Kogevinas, Manolis; Koller, Anna C.; Lavebratt, Catharina; Lucae, Susanne; Maaser, Anna; Martinsson, Lina; Montgomery, Grant W.; Morris, Derek W.; Mullins, Niamh; Nievergelt, Caroline M.; Adolfsson, Annelie Nordin; Loohuis, Loes M.O.; Perlis, Roy H.; Perry, Amy; Potash, James B.; Reinbold, Céline S.; Rivera, Margarita; Sigurdsson, Engilbert; Smeland, Olav B.; Streit, Fabian; Strohmaier, Jana; Thorgeirsson, Thorgeir E.; Treutlein, Jens; Witt, Stephanie H.; Zandi, Peter; Agartz, Ingrid; Alda, Martin; Backlund, Lena; Baune, Bernhard T.; Berrettini, Wade H.; Biernacka, Joanna M.; Blackwood, Douglas H. R.; Craddock, Nicholas; Dannlowski, Udo; Fullerton, Janice M.; Gershon, Elliot S.; Goes, Fernando S.; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Jones, Ian; Jones, Lisa A.; Lewis, Cathryn M.; Lissowska, Jolanta; Melle, Ingrid; Mitchell, Philip B.; Morken, Gunnar; Müller-Myhsok, Bertram; Nöthen, Markus M.; Ødegaard, Ketil J.; Owen, Michael J.; Paciga, Sara A.; Pato, Carlos; Pato, Michele T.; Rietschel, Marcella; Schalling, Martin; Schulze, Thomas G.; Serretti, Alessandro; Stordal, Eystein; Vaaler, Arne E.; Vieta, Eduard; Vincent, John B.; Florio, Arianna Di; Cichon, Sven; Ophoff, Roel A.; Scott, Laura J.; Adan, Roger A.H.; Alfredsson, Lars; Ando, Tetsuya; Aschauer, Harald; Baker, Jessica H.; Bencko, Vladimir; Bergen, Andrew W.; Birgegård, Andreas; Perica, Vesna Boraska; Brandt, Harry; Burghardt, Roland; Carlberg, Laura; Cassina, Matteo; Clementi, Maurizio; Courtet, Philippe; Crawford, Steven; Crow, Scott; Crowley, James J.; Danner, Unna N.; Davis, Oliver S.P.; Degortes, Daniela; DeSocio, Janiece E.; Dick, Danielle M.; Dina, Christian; Docampo, Elisa; Egberts, Karin; Ehrlich, Stefan; Espeseth, Thomas; Fernández-Aranda, Fernando; Fichter, Manfred M.; Foretova, Lenka; Forzan, Monica; Gambaro, Giovanni; Giegling, Ina; Gonidakis, Fragiskos; Gorwood, Philip; Mayora, Monica Gratacos; Guo, Yiran; Halmi, Katherine A.; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Hinney, Anke; Jiménez-Murcia, Susana; Johnson, Craig; Jordan, Jennifer; Kaminská, Deborah; Karhunen, Leila; Karwautz, Andreas; Kas, Martien J.H.; Kaye, Walter H.; L., Martin Kennedy; Kim, Youl-Ri; Klareskog, Lars; Klump, Kelly L.; Knudsen, Gun Peggy S.; Le Hellard, Mikael Landén-Stephanie; Levitan, Robert D.; Li, Dong; Lichtenstein, Paul; Maj, Mario; Marsal, Sara; McDevitt, Sara; Mitchell, James; Monteleone, Palmiero; Monteleone, Alessio Maria; Munn-Chernoff, Melissa A.; Nacmias, Benedetta; Navratilova, Marie; O’Toole, Julie K.; Padyukov, Leonid; Pantel, Jacques; Papezova, Hana; Rabionet, Raquel; Raevuori, Anu; Ramoz, Nicolas; Reichborn-Kjennerud, Ted; Ricca, Valdo; Roberts, Marion; Rujescu, Dan; Rybakowski, Filip; Scherag, André; Schmidt, Ulrike; Seitz, Jochen; Slachtova, Lenka; ’t Landt, Margarita C.T. Slof-Op; Slopien, Agnieszka; Sorbi, Sandro; Southam, Lorraine; Strober, Michael; Tortorella, Alfonso; Tozzi, Federica; Treasure, Janet; Tziouvas, Konstantinos; van Elburg, Annemarie A.; Wade, Tracey D.; Walton, Esther; Watson, Hunna J.; Wichmann, H-Erich; Woodside, D. Blake; Yilmaz, Zeynep; Zeggini, Eleftheria; Zerwas, Stephanie; Zipfel, Stephan; Adams, Mark J.; Andlauer, Till F.M.; Binder, Elisabeth B.; Castelao, Enrique; Colodro-Conde, Lucı́a; Direk, Nese; Docherty, Anna R.; Dunn, Erin C.; Foo, Jerome C.; Horn, Carsten; Hottenga, Jouke-Jan; Howard, David; Ising, Marcus; Mbarek, Hamdi; Middeldorp, Christel M.; Mostafavi, Sara; Peterson, Roseann E.; Pistis, Giorgio; Quiroz, Jorge A.; Schulte, Eva C.; Shi, Jianxin; Smith, Daniel J.; Thomson, Pippa A.; der Auwera, Sandra van; Berger, Klaus; Boomsma, Dorret I.; Geus, EJC de.; Domenici, Enrico; Domschke, Katharina; Grabe, Hans J.; Hamilton, Steven P.; Kloiber, Stefan; Lewis, Glyn; Li, Qingqin S.; Magnusson, Patrik K.; Penninx, Brenda WJH.; Porteous, David J.; Preisig, Martin; Schaefer, Catherine; Tiemeier, Henning; Uher, Rudolf; Weissman, Myrna M.; Levinson, Douglas F.; Barr, Cathy L.; Brown, Lawrence W.; Budman, Cathy; Coffey, Keun-Ah Cheon-Barbara J.; Davis, Lea K.; Dietrich, Andrea; Fernandez, Thomas V.; Garcia-Delgar, Blanca; Gilbert, Donald L.; Grados, Marco A.; Hagstrøm, Julie; Hartmann, Andreas; Hedderly, Tammy; Heiman, Gary A.; Hong, Isobel Heyman-Hyun Ju; Huyser, Chaim; Kim, Young Key; Kim, Young-Shin; King, Robert A.; Koh, Yun-Joo; Konstantinidis, Anastasios; Kook, Sodahm; Kuperman, Samuel; Leventhal, Bennett L.; Madruga-Garrido, Marcos; Maras, Athanasios; Mir, Pablo; Morer, Astrid; Müller-Vahl, Kirsten; Murphy, Tara L.; Münchau, Alexander; Paschou, Peter Nagy-Peristera; Pittenger, Christopher; Plessen, Kerstin J.; Rizzo, Renata; Robertson, Mary; Roessner, Veit; Sandor, Paul; Shin, Eun-Young; Song, Dong-Ho; Stuhrmann, Manfred; Tarnok-, Zsanett; Tischfield, Jay A.; Tübing, Jennifer; Visscher, Frank; Woods, Sina Wanderer-Martin; Zinner, Yulia Worbe-Samuel H.; Arnold, Valsamma Eapen-Paul D.; Bey, Katharina; Bienvenu, O. Joseph; Black, Donald; Ciullo, Valentina; Cusi, Danielle; Falkai, Damiaan Denys-Peter; Geller, Daniel A.; Grünblatt, Edna; Hanna, Gregory L.; Khramtsova, Ekaterina A.; McCracken, James T.; Meijer, Inge; Nestadt, Gerald; Nestadt, Paul S.; Nicolini, Humberto; Nurmi, Erika; Piras, Fabrizio; Piras, Federica; Richter, Margaret A.; Ruhrmann, Stephan; Samuels, Jack F.; Spalletta, Gianfranco; Stein, Dan J.; Stranger, Eric A. Storch-Barbara; Wagner, Nienke Vulink-Michael; Walitza, Susanne; Zai, Gwyneth; Bramon, Elvira; Buccola, Nancy G.; Cairns, Murray J.; Campion, Dominique; Carr, Vaughan J.; Cloninger, C. Robert; Donohoe, Gary; Freedman, Robert; Hartmann, Annette M.; Henskens, Frans A.; Ikeda, Masashi; Iwata, Nakao; Jablensky, Assen V.; Joa, Inge; Jönsson, Erik G.; Kelly, Brian J.; Knight, Jo; Konte, Bettina; Laurent-Levinson, Claudine; Lee, Jimmy; Lencz, Todd; Loughland, Carmel M.; Malhotra, Anil K.; McDonald, Colm; Mitjans, Marina; Mowry, Bryan J.; Murray, Robin M.; Os, Jim van; Pantelis, Christos; Endophenotypes International Consortium, Psychosis; Petryshen, Tracey L.; Quested, Digby J.; Sanders, Alan R.; Schall, Ulrich; Schwab, Sibylle G.; Scott, Rodney J.; Silverman, Jeremy M.; Steixner, Agnes A.; Tooney, Paul A.; Weiser, Mark; Wildenauer, Dieter B.; Trust Case-Control Consortium, Wellcome; Zhang, Fuquan; Sullivan, Patrick F.; Franke, Barbara; Daly, Mark J.; Bulik, Cynthia M.; McIntosh, Andrew M.; O’Donovan, Michael C.; Zheutlin, Amanda; Andreassen, Ole A.; Børglum, Anders D.; Breen, Gerome; Edenberg, Howard J.; Fanous, Ayman H.; Faraone, Stephen V.; Gelernter, Joel; Mathews, Carol A.; Mattheisen, Manuel; Mitchell, Karen; Nurnberger, Michael C. Neale-John I.; Ripke, Stephan; Santangelo, Susan L.; Scharf, Jeremiah M.; Thornton, Murray Stein-Laura M.; Walters, James T.R.; Wray, Naomi R.; Geschwind, Daniel H.; Neale, Benjamin; Kendler, Kenneth S.; Smoller, Jordan W.; Baldursson, Gisli; Pedersen, Carsten Bøcker; Lesch, Klaus-Peter J.; Hougaard, David Michael; Mortensen, Preben Bo; De Rubeis, Silvia; Forstner, Andreas Josef; Borglum, Anders D.; Neale, Michael C.; Nurnberger, John I.; Stein, Murray B.; Thornton, Laura M. |
| Publication Year: |
2019 |
| Collection: |
Publication Server of Goethe University Frankfurt am Main |
| Subject Terms: |
ddc:610 |
| Description: |
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed a meta-analysis of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders identifying three groups of inter-related disorders. We detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction. |
| Document Type: |
report |
| File Description: |
application/zip |
| Language: |
English |
| Relation: |
https://doi.org/10.1101/528117 |
| DOI: |
10.1101/528117 |
| Availability: |
http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73255; https://nbn-resolving.org/urn:nbn:de:hebis:30:3-732552; https://doi.org/10.1101/528117; http://publikationen.ub.uni-frankfurt.de/files/73255/container.zip |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.de ; info:eu-repo/semantics/restrictedAccess |
| Accession Number: |
edsbas.19DB41D3 |
| Database: |
BASE |