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  Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Mullins, N., Forstner, A. J., O'Connell, K. S., Coombes, B., Coleman I, J. R., Qiao, Z., et al. (2021). Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. NATURE GENETICS, 53(6), 817-829. doi:10.1038/s41588-021-00857-4.

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Mullins, Niamh, Author
Forstner, Andreas J., Author
O'Connell, Kevin S., Author
Coombes, Brandon, Author
Coleman I, Jonathan R., Author
Qiao, Zhen, Author
Als, Thomas D., Author
Bigdeli, Tim B., Author
Borte, Sigrid, Author
Bryois, Julien, Author
Charney, Alexander W., Author
Drange, Ole Kristian, Author
Gandal, Michael J., Author
Hagenaars, Saskia P., Author
Ikeda, Masashi, Author
Kamitaki, Nolan, Author
Kim, Minsoo, Author
Krebs, Kristi, Author
Panagiotaropoulou, Georgia, Author
Schilder, Brian M., Author
Sloofman, Laura G., AuthorSteinberg, Stacy, AuthorTrubetskoy, Vassily, AuthorWinsvold, Bendik S., AuthorWon, Hong-Hee, AuthorAbramova, Liliya, AuthorAdorjan, Kristina, AuthorAgerbo, Esben, AuthorAl Eissa, Mariam, AuthorAlbani, Diego, AuthorAlliey-Rodriguez, Ney, AuthorAnjorin, Adebayo, AuthorAntilla, Verneri, AuthorAntoniou, Anastasia, AuthorAwasthi, Swapnil, AuthorBaek, Ji Hyun, AuthorBaekvad-Hansen, Marie, AuthorBass, Nicholas, AuthorBauer, Michael, AuthorBeins, Eva C., AuthorBergen, Sarah E., AuthorBirner, Armin, AuthorPedersen, Carsten Bocker, AuthorBoen, Erlend, AuthorBoks, Marco P., AuthorBosch, Rosa, AuthorBrum, Murielle, AuthorBrumpton, Ben M., AuthorBrunkhorst-Kanaan, Nathalie, AuthorBudde, Monika, AuthorBybjerg-Grauholm, Jonas, AuthorByerley, William, AuthorCairns, Murray, AuthorCasas, Miquel, AuthorCervantes, Pablo, AuthorClarke, Toni-Kim, AuthorCruceanu, Cristiana1, Author           Cuellar-Barboza, Alfredo, AuthorCunningham, Julie, AuthorCurtis, David, AuthorCzerski, Piotr M., AuthorDale, Anders M., AuthorDalkner, Nina, AuthorDavid, Friederike S., AuthorDegenhardt, Franziska, AuthorDjurovic, Srdjan, AuthorDobbyn, Amanda L., AuthorDouzenis, Athanassios, AuthorElvsashagen, Torbjorn, AuthorEscott-Price, Valentina, AuthorFerrier, I. Nicol, AuthorFiorentino, Alessia, AuthorForoud, Tatiana M., AuthorForty, Liz, AuthorFrank, Josef, AuthorFrei, Oleksandr, AuthorFreimer, Nelson B., AuthorFrisen, Louise, AuthorGade, Katrin, AuthorGarnham, Julie, AuthorGelernter, Joel, AuthorPedersen, Marianne Giortz, AuthorGizer, Ian R., AuthorGordon, Scott D., AuthorGordon-Smith, Katherine, AuthorGreenwood, Tiffany A., AuthorGrove, Jakob, AuthorGuzman-Parra, Jose, AuthorHa, Kyooseob, AuthorHaraldsson, Magnus, AuthorHautzinger, Martin, AuthorHeilbronner, Urs, AuthorHellgren, Dennis, AuthorHerms, Stefan, AuthorHoffmann, Per, AuthorHolmans, Peter A., AuthorHuckins, Laura, AuthorJamain, Stephane, AuthorJohnson, Jessica S., AuthorKalman, Janos L.2, Author           Kamatani, Yoichiro, AuthorKennedy, James L., AuthorKittel-Schneider, Sarah, AuthorKnowles, James A., AuthorKogevinas, Manolis, AuthorKoromina, Maria, AuthorKranz, Thorsten M., AuthorKranzler, Henry R., AuthorKubo, Michiaki, AuthorKupka, Ralph, AuthorKushner, Steven A., AuthorLavebratt, Catharina, AuthorLawrence, Jacob, AuthorLeber, Markus, AuthorLee, Heon-Jeong, AuthorLee, Phil H., AuthorLevy, Shawn E., AuthorLewis, Catrin, AuthorLiao, Calwing, AuthorLucae, Susanne3, Author           Lundberg, Martin, AuthorMacIntyre, Donald J., AuthorMaier, Wolfgang, AuthorMaihofer, Adam, AuthorMalaspina, Dolores, AuthorMaratou, Eirini, AuthorMartinsson, Lina, AuthorMattheisen, Manuel, AuthorMcCarroll, Steven A., AuthorMcGregor, Nathaniel W., AuthorMcGuffin, Peter, AuthorMcKay, James D., AuthorMedeiros, Helena, AuthorMedland, Sarah E., AuthorMillischer, Vincent, AuthorMontgomery, Grant W., AuthorMoran, Jennifer L., AuthorMorris, Derek W., AuthorMuhleisen, Thomas W., AuthorO'Brien, Niamh, AuthorO'Donovan, Claire, AuthorLoohuis, Loes M. Olde, AuthorOruc, Lilijana, AuthorPapiol, Sergi, AuthorPardinas, Antonio F., AuthorPerry, Amy, AuthorPfennig, Andrea, AuthorPorichi, Evgenia, AuthorPotash, James B., AuthorQuested, Digby, AuthorRaj, Towfique, AuthorRapaport, Mark H., AuthorDePaulo, J. Raymond, AuthorRegeer, Eline J., AuthorRice, John P., AuthorRivas, Fabio, AuthorRivera, Margarita, AuthorRoth, Julian, AuthorRoussos, Panos, AuthorRuderfer, Douglas M., AuthorSanchez-Mora, Cristina, AuthorSchulte, Eva C., AuthorSenner, Fanny, AuthorSharp, Sally, AuthorShilling, Paul D., AuthorSigurdsson, Engilbert, AuthorSirignano, Lea, AuthorSlaney, Claire, AuthorSmeland, Olav B., AuthorSobell, Janet L., AuthorHansen, Christine Soholm, AuthorArtigas, Maria Soler, AuthorSpijker, Anne T., AuthorStein, Dan J., AuthorStrauss, John S., AuthorSwiatkowska, Beata, AuthorTerao, Chikashi, AuthorThorgeirsson, Thorgeir E., AuthorToma, Claudio, AuthorTooney, Paul, AuthorTsermpini, Evangelia-Eirini, AuthorVawter, Marquis P., AuthorVedder, Helmut, AuthorWalters, James T. R., AuthorWitt, Stephanie H., AuthorXi, Simon, AuthorXu, Wei, AuthorYang, Jessica Mei Kay, AuthorYoung, Allan H., AuthorYoung, Hannah, AuthorZandi, Peter P., AuthorZhou, Hang, AuthorZillich, Lea, AuthorAdolfsson, Rolf, AuthorAgartz, Ingrid, AuthorAlda, Martin, AuthorAlfredsson, Lars, AuthorBabadjanova, Gulja, AuthorBacklund, Lena, AuthorBaune, Bernhard T., AuthorBellivier, Frank, AuthorBengesser, Susanne, AuthorBerrettini, Wade H., AuthorBlackwood, Douglas H. R., AuthorBoehnke, Michael, AuthorBorglum, Anders D., AuthorBreen, Gerome, AuthorCarr, Vaughan J., AuthorCatts, Stanley, AuthorCorvin, Aiden, AuthorCraddock, Nicholas, AuthorDannlowski, Udo, AuthorDikeos, Dimitris, AuthorEsko, Tonu, AuthorEtain, Bruno, AuthorFerentinos, Panagiotis, AuthorFrye, Mark, AuthorFullerton, Janice M., AuthorGawlik, Micha, AuthorGershon, Elliot S., AuthorGoes, Fernando, AuthorGreen, Melissa J., AuthorGrigoroiu-Serbanescu, Maria, AuthorHauser, Joanna, AuthorHenskens, Frans, AuthorHillert, Jan, AuthorHong, Kyung Sue, AuthorHougaard, David M., AuthorHultman, Christina M., AuthorHveem, Kristian, AuthorIwata, Nakao, AuthorJablensky V, Assen, AuthorJones, Ian, AuthorJones, Lisa A., AuthorKahn, Rene S., AuthorKelsoe, John R., AuthorKirov, George, AuthorLanden, Mikael, AuthorLeboyer, Marion, AuthorLewis, Cathryn M., AuthorLi, Qingqin S., AuthorLissowska, Jolanta, AuthorLochner, Christine, AuthorLoughland, Carmel, AuthorMartin, Nicholas G., AuthorMathews, Carol A., AuthorMayoral, Fermin, AuthorMcElroy, Susan L., AuthorMcIntosh, Andrew M., AuthorMcMahon, Francis J., AuthorMelle, Ingrid, AuthorMichie, Patricia, AuthorMilani, Lili, AuthorMitchell, Philip B., AuthorMorken, Gunnar, AuthorMors, Ole, AuthorMortensen, Preben Bo, AuthorMowry, Bryan, AuthorMuller-Myhsok, Bertram4, Author           Myers, Richard M., AuthorNeale, Benjamin M., AuthorNievergelt, Caroline M., AuthorNordentoft, Merete, AuthorNothen, Markus M., AuthorODonovan, Michael C., AuthorOedegaard, Ketil J., AuthorOlsson, Tomas, AuthorOwen, Michael J., AuthorPaciga, Sara A., AuthorPantelis, Chris, AuthorPato, Carlos, AuthorPato, Michele T., AuthorPatrinos, George P., AuthorPerlis, Roy H., AuthorPosthuma, Danielle, AuthorRamos-Quiroga, Josep Antoni, AuthorReif, Andreas, AuthorReininghaus, Eva Z., AuthorRibases, Marta, AuthorRietschel, Marcella, AuthorRipke, Stephan, AuthorRouleau, Guy A., AuthorSaito, Takeo, AuthorSchall, Ulrich, AuthorSchalling, Martin, AuthorSchofield, Peter R., AuthorSchulze, Thomas G., AuthorScott, Laura J., AuthorScott, Rodney J., AuthorSerretti, Alessandro, AuthorWeickert, Cynthia Shannon, AuthorSmoller, Jordan W., AuthorStefansson, Hreinn, AuthorStefansson, Kari, AuthorStordal, Eystein, AuthorStreit, Fabian, AuthorSullivan, Patrick F., AuthorTurecki, Gustavo, AuthorVaaler, Arne E., AuthorVieta, Eduard, AuthorVincent, John B., AuthorWaldman, Irwin D., AuthorWeickert, Thomas W., AuthorWerge, Thomas, AuthorWray, Naomi R., AuthorZwart, JohnAnker, AuthorBiernacka, Joanna M., AuthorNurnberger I, John, AuthorCichon, Sven, AuthorEdenberg, Howard J., AuthorStahl, Eli A., AuthorMcQuillin, Andrew, AuthorDi Florio, Arianna, AuthorOphoff, Roel A., AuthorAndreassen, Ole A., Author more..
Affiliations:
1Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              
2IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_3318616              
3Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              
4RG Statistical Genetics, Max Planck Institute of Psychiatry, Max Planck Society, ou_2040288              

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 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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 Dates: 2021
 Publication Status: Published in print
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Title: NATURE GENETICS
Source Genre: Journal
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Pages: - Volume / Issue: 53 (6) Sequence Number: - Start / End Page: 817 - 829 Identifier: ISSN: 1061-4036