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Cited 389 time in webofscience Cited 424 time in scopus
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Authors
Mullins, NiamhForstner, Andreas J.O'Connell, Kevin S.Coombes, BrandonColeman, Jonathan R., IQiao, ZhenAls, Thomas D.Bigdeli, Tim B.Borte, SigridBryois, JulienCharney, Alexander W.Drange, Ole KristianGandal, Michael J.Hagenaars, Saskia P.Ikeda, MasashiKamitaki, NolanKim, MinsooKrebs, KristiPanagiotaropoulou, GeorgiaSchilder, Brian M.Sloofman, Laura G.Steinberg, StacyTrubetskoy, VassilyWinsvold, Bendik S.Won, Hong-HeeAbramova, LiliyaAdorjan, KristinaAgerbo, EsbenAl Eissa, MariamAlbani, DiegoAlliey-Rodriguez, NeyAnjorin, AdebayoAntilla, VerneriAntoniou, AnastasiaAwasthi, SwapnilBaek, Ji HyunBaekvad-Hansen, MarieBass, NicholasBauer, MichaelBeins, Eva C.Bergen, Sarah E.Birner, ArminPedersen, Carsten BockerBoen, ErlendBoks, Marco P.Bosch, RosaBrum, MurielleBrumpton, Ben M.Brunkhorst-Kanaan, NathalieBudde, MonikaBybjerg-Grauholm, JonasByerley, WilliamCairns, MurrayCasas, MiquelCervantes, PabloClarke, Toni-KimCruceanu, CristianaCuellar-Barboza, AlfredoCunningham, JulieCurtis, DavidCzerski, Piotr M.Dale, Anders M.Dalkner, NinaDavid, Friederike S.Degenhardt, FranziskaDjurovic, SrdjanDobbyn, Amanda L.Douzenis, AthanassiosElvsashagen, TorbjornEscott-Price, ValentinaFerrier, I. NicolFiorentino, AlessiaForoud, Tatiana M.Forty, LizFrank, JosefFrei, OleksandrFreimer, Nelson B.Frisen, LouiseGade, KatrinGarnham, JulieGelernter, JoelPedersen, Marianne GiortzGizer, Ian R.Gordon, Scott D.Gordon-Smith, KatherineGreenwood, Tiffany A.Grove, JakobGuzman-Parra, JoseHa, KyooseobHaraldsson, MagnusHautzinger, MartinHeilbronner, UrsHellgren, DennisHerms, StefanHoffmann, PerHolmans, Peter A.Huckins, LauraJamain, StephaneJohnson, Jessica S.Kalman, Janos L.Kamatani, YoichiroKennedy, James L.Kittel-Schneider, SarahKnowles, James A.Kogevinas, ManolisKoromina, MariaKranz, Thorsten M.Kranzler, Henry R.Kubo, MichiakiKupka, RalphKushner, Steven A.Lavebratt, CatharinaLawrence, JacobLeber, MarkusLee, Heon-JeongLee, Phil H.Levy, Shawn E.Lewis, CatrinLiao, CalwingLucae, SusanneLundberg, MartinMacIntyre, Donald J.Maier, WolfgangMaihofer, AdamMalaspina, DoloresMaratou, EiriniMartinsson, LinaMattheisen, ManuelMcCarroll, Steven A.McGregor, Nathaniel W.McGuffin, PeterMcKay, James D.Medeiros, HelenaMedland, Sarah E.Millischer, VincentMontgomery, Grant W.Moran, Jennifer L.Morris, Derek W.Muhleisen, Thomas W.O'Brien, NiamhO'Donovan, ClaireLoohuis, Loes M. OldeOruc, LilijanaPapiol, SergiPardinas, Antonio F.Perry, AmyPfennig, AndreaPorichi, EvgeniaPotash, James B.Quested, DigbyRaj, TowfiqueRapaport, Mark H.DePaulo, J. RaymondRegeer, Eline J.Rice, John P.Rivas, FabioRivera, MargaritaRoth, JulianRoussos, PanosRuderfer, Douglas M.Sanchez-Mora, CristinaSchulte, Eva C.Senner, FannySharp, SallyShilling, Paul D.Sigurdsson, EngilbertSirignano, LeaSlaney, ClaireSmeland, Olav B.Sobell, Janet L.Hansen, Christine SoholmArtigas, Maria SolerSpijker, Anne T.Stein, Dan J.Strauss, John S.Swiatkowska, BeataTerao, ChikashiThorgeirsson, Thorgeir E.Toma, ClaudioTooney, PaulTsermpini, Evangelia-EiriniVawter, Marquis P.Vedder, HelmutWalters, James T. R.Witt, Stephanie H.Xi, SimonXu, WeiYang, Jessica Mei KayYoung, Allan H.Young, HannahZandi, Peter P.Zhou, HangZillich, LeaAdolfsson, RolfAgartz, IngridAlda, MartinAlfredsson, LarsBabadjanova, GuljaBacklund, LenaBaune, Bernhard T.Bellivier, FrankBengesser, SusanneBerrettini, Wade H.Blackwood, Douglas H. R.Boehnke, MichaelBorglum, Anders D.Breen, GeromeCarr, Vaughan J.Catts, StanleyCorvin, AidenCraddock, NicholasDannlowski, UdoDikeos, DimitrisEsko, TonuEtain, BrunoFerentinos, PanagiotisFrye, MarkFullerton, Janice M.Gawlik, MichaGershon, Elliot S.Goes, FernandoGreen, Melissa J.Grigoroiu-Serbanescu, MariaHauser, JoannaHenskens, FransHillert, JanHong, Kyung SueHougaard, David M.Hultman, Christina M.Hveem, KristianIwata, NakaoJablensky, Assen, VJones, IanJones, Lisa A.Kahn, Rene S.Kelsoe, John R.Kirov, GeorgeLanden, MikaelLeboyer, MarionLewis, Cathryn M.Li, Qingqin S.Lissowska, JolantaLochner, ChristineLoughland, CarmelMartin, Nicholas G.Mathews, Carol A.Mayoral, FerminMcElroy, Susan L.McIntosh, Andrew M.McMahon, Francis J.Melle, IngridMichie, PatriciaMilani, LiliMitchell, Philip B.Morken, GunnarMors, OleMortensen, Preben BoMowry, BryanMuller-Myhsok, BertramMyers, Richard M.Neale, Benjamin M.Nievergelt, Caroline M.Nordentoft, MereteNothen, Markus M.ODonovan, Michael C.Oedegaard, Ketil J.Olsson, TomasOwen, Michael J.Paciga, Sara A.Pantelis, ChrisPato, CarlosPato, Michele T.Patrinos, George P.Perlis, Roy H.Posthuma, DanielleRamos-Quiroga, Josep AntoniReif, AndreasReininghaus, Eva Z.Ribases, MartaRietschel, MarcellaRipke, StephanRouleau, Guy A.Saito, TakeoSchall, UlrichSchalling, MartinSchofield, Peter R.Schulze, Thomas G.Scott, Laura J.Scott, Rodney J.Serretti, AlessandroWeickert, Cynthia ShannonSmoller, Jordan W.Stefansson, HreinnStefansson, KariStordal, EysteinStreit, FabianSullivan, Patrick F.Turecki, GustavoVaaler, Arne E.Vieta, EduardVincent, John B.Waldman, Irwin D.Weickert, Thomas W.Werge, ThomasWray, Naomi R.Zwart, JohnAnkerBiernacka, Joanna M.Nurnberger, John, ICichon, SvenEdenberg, Howard J.Stahl, Eli A.McQuillin, AndrewDi Florio, AriannaOphoff, Roel A.Andreassen, Ole A.
Issue Date
Jun-2021
Publisher
NATURE RESEARCH
Citation
NATURE GENETICS, v.53, no.6, pp 817 - 829
Pages
13
Indexed
SCIE
SCOPUS
Journal Title
NATURE GENETICS
Volume
53
Number
6
Start Page
817
End Page
829
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/53358
DOI
10.1038/s41588-021-00857-4
ISSN
1061-4036
1546-1718
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. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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Lee, Heon Jeong
Anam Hospital (Department of Psychiatry, Anam Hospital)
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