Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder
Author:
Stahl Eli AORCID, Breen GeromeORCID, Forstner Andreas JORCID, McQuillin AndrewORCID, Ripke StephanORCID, Trubetskoy Vassily, Mattheisen Manuel, Wang Yunpeng, Coleman Jonathan R I, Gaspar Héléna A, de Leeuw Christiaan A, Steinberg Stacy, Whitehead Pavlides Jennifer M, Trzaskowski Maciej, Pers Tune H, Holmans Peter A, Abbott Liam, Agerbo Esben, Akil Huda, Albani Diego, Alliey-Rodriguez Ney, Als Thomas D, Anjorin Adebayo, Antilla Verneri, Awasthi Swapnil, Badner Judith A, Bækvad-Hansen Marie, Barchas Jack D, Bass Nicholas, Bauer Michael, Belliveau Richard, Bergen Sarah E, Bøcker Pedersen Carsten, Bøen Erlend, Boks Marco, Boocock James, Budde Monika, Bunney William, Burmeister Margit, Bybjerg-Grauholm Jonas, Byerley William, Casas Miquel, Cerrato Felecia, Cervantes Pablo, Chambert Kimberly, Charney Alexander W, Chen Danfeng, Churchhouse Claire, Clarke Toni-Kim, Coryell William, Craig David W, Cruceanu Cristiana, Curtis David, Czerski Piotr M, Dale Anders M, de Jong Simone, Degenhardt Franziska, Del-Favero Jurgen, DePaulo J Raymond, Djurovic Srdjan, Dobbyn Amanda L, Dumont Ashley, Elvsåshagen Torbjørn, Escott-Price Valentina, Fan Chun Chieh, Fischer Sascha B, Flickinger Matthew, Foroud Tatiana M, Forty Liz, Frank Josef, Fraser Christine, Freimer Nelson B, Frisén Louise, Gade Katrin, Gage Diane, Garnham Julie, Giambartolomei Claudia, Giørtz Pedersen Marianne, Goldstein Jaqueline, Gordon Scott D, Gordon-Smith Katherine, Green Elaine K, Green Melissa J, Greenwood Tiffany A, Grove Jakob, Guan Weihua, Parra JoséGuzman, Hamshere Marian L, Hautzinger Martin, Heilbronner Urs, Herms Stefan, Hipolito Maria, Hoffmann Per, Holland Dominic, Huckins Laura, Jamain Stéphane, Johnson Jessica S, Juréus Anders, Kandaswamy Radhika, Karlsson Robert, Kennedy James L, Kittel-Schneider Sarah, Knott Sarah V, Knowles James A, Kogevinas Manolis, Koller Anna C, Kupka Ralph, Lavebratt Catharina, Lawrence Jacob, Lawson William B, Leber Markus, Lee Phil H, Levy Shawn E, Li Jun Z, Liu Chunyu, Lucae Susanne, Maaser Anna, MacIntyre Donald J, Mahon Pamela B, Maier Wolfgang, Martinsson Lina, McCarroll Steve, McGuffin Peter, McInnis Melvin G, McKay James D, Medeiros Helena, Medland Sarah E, Meng Fan, Milani Lili, Montgomery Grant W, Morris Derek W, Mühleisen Thomas W, Mullins Niamh, Nguyen Hoang, Nievergelt Caroline M, Adolfsson Annelie Nordin, Nwulia Evaristus A, O’Donovan Claire, Olde Loohuis Loes M, Ori Anil P S, Oruc Lilijana, Ösby Urban, Perlis Roy H, Perry Amy, Pfennig Andrea, Potash James B, Purcell Shaun M, Regeer Eline J, Reif Andreas, Reinbold Céline S, Rice John P, Rivas Fabio, Rivera Margarita, Roussos Panos, Ruderfer Douglas M, Ryu Euijung, Sánchez-Mora Cristina, Schatzberg Alan F, Scheftner William A, Schork Nicholas J, Weickert Cynthia Shannon, Shehktman Tatyana, Shilling Paul D, Sigurdsson Engilbert, Slaney Claire, Smeland Olav B, Sobell Janet L, Søholm Hansen Christine, Spijker Anne T, St Clair David, Steffens Michael, Strauss John S, Streit Fabian, Strohmaier Jana, Szelinger Szabolcs, Thompson Robert C, Thorgeirsson Thorgeir E, Treutlein Jens, Vedder Helmut, Wang Weiqing, Watson Stanley J, Weickert Thomas W, Witt Stephanie H, Xi Simon, Xu Wei, Young Allan H, Zandi Peter, Zhang Peng, Zollner Sebastian, Adolfsson Rolf, Agartz Ingrid, Alda Martin, Backlund Lena, Baune Bernhard T, Bellivier Frank, Berrettini Wade H, Biernacka Joanna M, Blackwood Douglas H R, Boehnke Michael, Børglum Anders D, Corvin Aiden, Craddock Nicholas, Daly Mark J, Dannlowski Udo, Esko Tõnu, Etain Bruno, Frye Mark, Fullerton Janice M, Gershon Elliot S, Gill Michael, Goes Fernando, Grigoroiu-Serbanescu Maria, Hauser Joanna, Hougaard David M, Hultman Christina M, Jones Ian, Jones Lisa A, Kahn RenéS, Kirov George, Landén Mikael, Leboyer Marion, Lewis Cathryn M, Li Qingqin S, Lissowska Jolanta, Martin Nicholas G, Mayoral Fermin, McElroy Susan L, McIntosh Andrew M, McMahon Francis J, Melle Ingrid, Metspalu Andres, Mitchell Philip B, Morken Gunnar, Mors Ole, Mortensen Preben Bo, Müller-Myhsok Bertram, Myers Richard M, Neale Benjamin M, Nimgaonkar Vishwajit, Nordentoft Merete, Nöthen Markus M, O’Donovan Michael C, Oedegaard Ketil J, Owen Michael J, Paciga Sara A, Pato Carlos, Pato Michele T, Posthuma Danielle, Ramos-Quiroga Josep Antoni, Ribasés Marta, Rietschel Marcella, Rouleau Guy A, Schalling Martin, Schofield Peter R, Schulze Thomas G, Serretti Alessandro, Smoller Jordan W, Stefansson Hreinn, Stefansson Kari, Stordal Eystein, Sullivan Patrick F, Turecki Gustavo, Vaaler Arne E, Vieta Eduard, Vincent John B, Werge Thomas, Nurnberger John I, Wray Naomi R, Di Florio Arianna, Edenberg Howard J, Cichon SvenORCID, Ophoff Roel AORCID, Scott Laura JORCID, Andreassen Ole AORCID, Kelsoe JohnORCID, Sklar PamelaORCID
Abstract
ABSTRACTBipolar disorder is a highly heritable psychiatric disorder that features episodes of mania and depression. We performed the largest genome-wide association study to date, including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 sentinel variants at loci with P<1×10-4 in an independent sample of 9,412 cases and 137,760 controls. In the combined analysis, 30 loci reached genome-wide significant evidence for association, of which 20 were novel. These significant loci contain genes encoding ion channels and neurotransmitter transporters (CACNA1C, GRIN2A, SCN2A, SLC4A1), synaptic components (RIMS1, ANK3), immune and energy metabolism components. Bipolar disorder type I (depressive and manic episodes; ~73% of our cases) is strongly genetically correlated with schizophrenia whereas bipolar disorder type II (depressive and hypomanic episodes; ~17% of our cases) is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for bipolar disorder.
Publisher
Cold Spring Harbor Laboratory
Cited by
34 articles.
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