Abstract

) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

Authors	Stahl, Eli A; Breen, Gerome; Forstner, Andreas J; McQuillin, Andrew; Ripke, Stephan; Trubetskoy, Vassily; Mattheisen, Manuel; Wang, Yunpeng; Coleman, Jonathan R I; Gaspar, Héléna A; de Leeuw, Christiaan A; Steinberg, Stacy; Pavlides, Jennifer M Whitehead; Trzaskowski, Maciej; Byrne, Enda M; Pers, Tune H; Holmans, Peter A; Richards, Alexander L; 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; Pedersen, Carsten Bøcker; Bøen, Erlend; Boks, Marco P; 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; Pedersen, Marianne Giørtz; Goldstein, Jaqueline; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Green, Melissa J; Greenwood, Tiffany A; Grove, Jakob; Guan, Weihua; Guzman-Parra, José; 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; 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; Loohuis, Loes M Olde; 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; Shannon Weickert, Cynthia; 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; Zöllner, 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, René S; 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, Sven; Ophoff, Roel A; Scott, Laura J; Andreassen, Ole A; Kelsoe, John; Sklar, Pamela; ,
Journal	NATURE GENETICS
Pages	793-803
Volume	51
Date	1/05/2019
Grant ID
Funding Body	US National Institute of Mental Health
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41588-019-0397-8
	Download Article