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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Authors :
Niamh, Mullins Andreas J, Forstner Kevin S, O'Connell Brandon, Coombes Jonathan R I, Coleman Zhen, Qiao Thomas D, Als Tim B, Bigdeli Sigrid, Børte Julien, Bryois Alexander W, Charney Ole Kristian, Drange Michael J, Gandal Saskia P, Hagenaars Masashi, Ikeda Nolan, Kamitaki Minsoo, Kim Kristi, Krebs Georgia, Panagiotaropoulou Brian M, Schilder Laura G, Sloofman Stacy, Steinberg Vassily, Trubetskoy Bendik S, Winsvold Hong-Hee, Won Liliya, Abramova Kristina, Adorjan Esben, Agerbo Mariam, Al Eissa Diego, Albani Ney, Alliey-Rodriguez Adebayo, Anjorin Verneri, Antilla Anastasia, Antoniou Swapnil, Awasthi Ji Hyun, Baek Marie, Bækvad-Hansen Nicholas, Bass Michael, Bauer Eva C, Beins Sarah E, Bergen Armin, Birner Carsten, Bøcker Pedersen Erlend, Bøen Marco P, Boks Rosa, Bosch Murielle, Brum Ben M, Brumpton Nathalie, Brunkhorst-Kanaan Monika, Budde Jonas, Bybjerg-Grauholm William, Byerley Murray, Cairns Miquel, Casas Pablo, Cervantes Toni-Kim, Clarke Cristiana, Cruceanu Alfredo, Cuellar-Barboza Julie, Cunningham David, Curtis Piotr M, Czerski Anders M, Dale Nina, Dalkner Friederike S, David Franziska, Degenhardt Srdjan, Djurovic Amanda L, Dobbyn Athanassios, Douzenis Torbjørn, Elvsåshagen Valentina, Escott-Price I Nicol, Ferrier Alessia, Fiorentino Tatiana M, Foroud Liz, Forty Josef, Frank Oleksandr, Frei Nelson B, Freimer Louise, Frisén Katrin, Gade Julie, Garnham Joel, Gelernter Marianne, Giørtz Pedersen Ian R, Gizer Scott D, Gordon Katherine, Gordon-Smith Tiffany A, Greenwood Jakob, Grove José, Guzman-Parra Kyooseob, Ha Magnus, Haraldsson Martin, Hautzinger Urs, Heilbronner Dennis, Hellgren Stefan, Herms Per, Hoffmann Peter A, Holmans Laura, Huckins Stéphane, Jamain Jessica S, Johnson Janos L, Kalman Yoichiro, Kamatani James L, Kennedy Sarah, Kittel-Schneider James A, Knowles Manolis, Kogevinas Maria, Koromina Thorsten M, Kranz Henry R, Kranzler Michiaki, Kubo Ralph, Kupka Steven A, Kushner Catharina, Lavebratt Jacob, Lawrence Markus, Leber Heon-Jeong, Lee Phil H, Lee Shawn E, Levy Catrin, Lewis Calwing, Liao Susanne, Lucae Martin, Lundberg Donald J, MacIntyre Sigurdur H, Magnusson Wolfgang, Maier Adam, Maihofer Dolores, Malaspina Eirini, Maratou Lina, Martinsson Manuel, Mattheisen Steven A, McCarroll Nathaniel W, McGregor Peter, McGuffin James D, McKay Helena, Medeiros Sarah E, Medland Vincent, Millischer Grant W, Montgomery Jennifer L, Moran Derek W, Morris Thomas W, Mühleisen Niamh, O'Brien Claire, O'Donovan Loes M, Olde Loohuis Lilijana, Oruc Sergi, Papiol Antonio F, Pardiñas Amy, Perry Andrea, Pfennig Evgenia, Porichi James B, Potash Digby, Quested Towfique, Raj Mark H, Rapaport J Raymond, DePaulo Eline J, Regeer John P, Rice Fabio, Rivas Margarita, Rivera Julian, Roth Panos, Roussos Douglas M, Ruderfer Cristina, Sánchez-Mora Eva C, Schulte Fanny, Senner Sally, Sharp Paul D, Shilling Engilbert, Sigurdsson Lea, Sirignano Claire, Slaney Olav B, Smeland Daniel J, Smith Janet L, Sobell Christine, Søholm Hansen Maria, Soler Artigas Anne T, Spijker Dan J, Stein John S, Strauss Beata, Świątkowska Chikashi, Terao Thorgeir E, Thorgeirsson Claudio, Toma Paul, Tooney Evangelia-Eirini, Tsermpini Marquis P, Vawter Helmut, Vedder James T R, Walters Stephanie H, Witt Simon, Xi Wei, Xu Jessica Mei Kay, Yang Allan H, Young Hannah, Young Peter P, Zandi Hang, Zhou Lea, Zillich Rolf, Adolfsson Ingrid, Agartz Martin, Alda Lars, Alfredsson Gulja, Babadjanova Lena, Backlund Bernhard T, Baune Frank, Bellivier Susanne, Bengesser Wade H, Berrettini Douglas H R, Blackwood Michael, Boehnke Anders D, Børglum Gerome, Breen Vaughan J, Carr Stanley, Catts Aiden, Corvin Nicholas, Craddock Udo, Dannlowski Dimitris, Dikeos Tõnu, Esko Bruno, Etain Panagiotis, Ferentinos Mark, Frye Janice M, Fullerton Micha, Gawlik Elliot S, Gershon Fernando S, Goes Melissa J, Green Maria, Grigoroiu-Serbanescu Joanna, Hauser Frans, Henskens Jan, Hillert Kyung Sue, Hong David M, Hougaard Christina M, Hultman Kristian, Hveem Nakao, Iwata Assen V, Jablensky Ian, Jones Lisa A, Jones René S, Kahn John R, Kelsoe George, Kirov Mikael, Landén Marion, Leboyer Cathryn M, Lewis Qingqin S, Li Jolanta, Lissowska Christine, Lochner Carmel, Loughland Nicholas G, Martin Carol A, Mathews Fermin, Mayoral Susan L, McElroy Andrew M, McIntosh Francis J, McMahon Ingrid, Melle Patricia, Michie Lili, Milani Philip B, Mitchell Gunnar, Morken Ole, Mors Preben Bo, Mortensen Bryan, Mowry Bertram, Müller-Myhsok Richard M, Myers Benjamin M, Neale Caroline M, Nievergelt Merete, Nordentoft Markus M, Nöthen Michael C, O'Donovan Ketil J, Oedegaard Tomas, Olsson Michael J, Owen Sara A, Paciga Chris, Pantelis Carlos, Pato Michele T, Pato George P, Patrinos Roy H, Perlis Danielle, Posthuma Josep Antoni, Ramos-Quiroga Andreas, Reif Eva Z, Reininghaus Marta, Ribasés Marcella, Rietschel Stephan, Ripke Guy A, Rouleau Takeo, Saito Ulrich, Schall Martin, Schalling Peter R, Schofield Thomas G, Schulze Laura J, Scott Rodney J, Scott Alessandro, Serretti Cynthia, Shannon Weickert Jordan W, Smoller Hreinn, Stefansson Kari, Stefansson Eystein, Stordal Fabian, Streit Patrick F, Sullivan Gustavo, Turecki Arne E, Vaaler Eduard, Vieta John B, Vincent Irwin D, Waldman Thomas W, Weickert Thomas, Werge Naomi R, Wray John-Anker, Zwart Joanna M, Biernacka John I, Nurnberger Sven, Cichon Howard J, Edenberg Eli A, Stahl Andrew, McQuillin Arianna, Di Florio Roel A, Ophoff Ole A, Andreassen
Source :
Nature genetics . 53(6)
Publication Year :
2020
Abstract
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
Details
ISSN :
15461718
Volume :
53
Issue :
6
Database :
OpenAIRE
Journal :
Nature genetics
Accession number :
edsair.pmid..........25975169e4fa7dbd4310c2e78e5a0279