“Genome-Wide Association Study Identifies 30 Loci Associated With Bipolar Disorder”, Eli Ayumi Stahl, Andreas J. Forstner, Andrew McQuillin, Stephan Ripke, Vassily Trubetskoy, Manuel Mattheisen, Weiqing Wang, Yunpeng Wang, Jonathan R. I. Coleman, Héléna A. Gaspar, Christiaan A. de Leeuw, Jennifer M. Whitehead Pavlides, Loes M. Olde Loohuis, Anil P. S. Ori, Tune H. Pers, Peter A. Holmans, Douglas M. Ruderfer, Phil H. Lee, Alexander W. Charney, Amanda L. Dobbyn, Laura Huckins, James Boocock, Claudia Giambartolomei, Panos Roussos, Niamh Mullins, Swapnil Awasthi, Esben Agerbo, Thomas D. Als, Carsten Bøcker Pedersen, Jakob Grove, Ralph Kupka, Eline J. Regeer, Adebayo Anjorin, Miquel Casas, Cristina Sánchez-Mora, Pamela B. Mahon, Shaun M. Purcell, Steve McCarroll, Judith Allardyce, Valentina Escott-Price, Liz Forty, Christine Fraser, Marian L. Hamshere, George Kirov, Manolis Kogevinas, Josef Frank, Fabian Streit, Jana Strohmaier, Jens Treutlein, Stephanie H. Witt, James L. Kennedy, John S. Strauss, Julie Garnham, Claire O’Donovan, Claire Slaney, Stacy Steinberg, Thorgeir E. Thorgeirsson, Martin Hautzinger, Michael Steffens, Ralph Kupka, Steve McCarroll, Roy H. Perlis, Miquel Casas, Cristina Sánchez-Mora, Maria Hipolito, William B. Lawson, Evaristus A. Nwulia, Shawn E. Levy, Shaun M. Purcell, Tatiana M. Foroud, Stéphane Jamain, Allan H. Young, James D. McKay, Thomas D. Als, Carsten Bøcker Pedersen, Jakob Grove, Diego Albani, Peter Zandi, Pamela B. Mahon, James B. Potash, Peng Zhang, J. Raymond DePaulo, Sarah E. Bergen, Anders Juréus, Robert Karlsson, Radhika Kandaswamy, Peter McGuffin, Margarita Rivera, Jolanta Lissowska, Roy H. Perlis, Cristiana Cruceanu, Susanne Lucae, Pablo Cervantes, Monika Budde, Katrin Gade, Urs Heilbronner, Marianne Giørtz Pedersen, Carsten Bøcker Pedersen, Derek W. Morris, Cynthia Shannon Weickert, Thomas W. Weickert, Donald J. MacIntyre, Jacob Lawrence, Torbjørn Elvsåshagen, Olav B. Smeland, Srdjan Djurovic, Simon Xi, Elaine K. Green, Piotr M. Czerski, Joanna Hauser, Wei Xu, Helmut Vedder, Lilijana Oruc, Anne T. Spijker, Scott D. Gordon, Sarah E. Medland, David Curtis, Thomas W. Mühleisen, Judith Badner, William A. Scheftner, Engilbert Sigurdsson, Nicholas J. Schork, Alan F. Schatzberg, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, Christine Søholm Hansen, James A. Knowles, Helena Medeiros, Szabolcs Szelinger, Grant W. Montgomery, Derek W. Morris, Marco Boks, Annelie Nordin Adolfsson, Miquel Casas, Stéphane Jamain, Nicholas Bass, David Curtis, Per Hoffmann, Michael Bauer, Andrea Pfennig, Markus Leber, Sarah Kittel-Schneider, Andreas Reif, Katrin Gade, Jurgen Del-Favero, Sascha B. Fischer, Stefan Herms, Per Hoffmann, Thomas W. Mühleisen, Céline S. Reinbold, Srdjan Djurovic, Franziska Degenhardt, Stefan Herms, Per Hoffmann, Anna C. Koller, Anna Maaser, Wolfgang Maier, Nelson B. Freimer, Anil Ori, Anders Martin Dale, Chun Chieh Fan, Tiffany A. Greenwood, Caroline M. Nievergelt, Tatyana Shehktman, Paul D. Shilling, Olav B. Smeland, William Byerley, William Bunney, Ney Alliey-Rodriguez, Douglas H. R. Blackwood, Toni-Kim Clarke, Donald J. MacIntyre, Margarita Rivera, Chunyu Liu, William Coryell, Huda Akil, Margit Burmeister, Matthew Flickinger, Jun Z. Li, Melvin G. McInnis, Fan Meng, Robert C. Thompson, Stanley J. Watson, Sebastian Zollner, Weihua Guan, Melissa J. Green, Cynthia Shannon Weickert, Thomas W. Weickert, Olav B. Smeland, David Craig, Janet L. Sobell, Lili Milani, James L. Kennedy, John S. Strauss, Wei Xu, Katherine Gordon-Smith, Sarah V. Knott, Amy Perry, José Guzman Parra, Fermin Mayoral, Fabio Rivas, Miquel Casas, Cristina Sánchez-Mora, Caroline M. Nievergelt, Ralph Kupka, John P. Rice, Jack D. Barchas, Anders Børglum, Preben Bo Mortensen, Ole Mors, Maria Grigoroiu-Serbanescu, Frank Bellivier, Bruno Etain, Marion Leboyer, Josep Antoni Ramos-Quiroga, Marta Ribasés, Tõnu Esko, Jordan W. Smoller, Nicholas Craddock, Ian Jones, Michael J. Owen, Marcella Rietschel, Thomas G. Schulze, John Vincent, Tõnu Esko, Eduard Vieta, Merete Nordentoft, Martin Alda, Hreinn Stefansson, Kari Stefansson, Danielle Posthuma, Ingrid Agartz, Frank Bellivier, Tõnunu Esko, Ketil J. Oedegaard, Eystein Stordal, Josep Antoni Ramos-Quiroga, Marta Ribasés, Richard M. Myers, René S. Kahn, Frank Bellivier, Bruno Etain, Marion Leboyer, Bruno Etain, Anders Børglum, Ole Mors, Thomas Werge, Qingqin S. Li, Thomas G. Schulze, Fernando Goes, Ingrid Agartz, Christina M. Hultman, Mikael Landén, Patrick F. Sullivan, Cathryn M. Lewis, Susan L. McElroy, Jordan W. Smoller, Bertram Müller-Myhsok, Joanna M. Biernacka, Mark Frye, Gustavo Turecki, Guy A. Rouleau, Thomas G. Schulze, Thomas Werge, Guy A. Rouleau, Bertram Müller-Myhsok, Martin Alda, Francis J. McMahon, Thomas G. Schulze, Janice M. Fullerton, Peter R. Schofield, Eystein Stordal, Gunnar Morken, Ulrik F. Malt, Ingrid Sigfrid Melle, Sara A. Paciga, Nicholas G. Martin, Arne E. Vaaler, Gunnar Morken, David Hougaard, Carlos Pato, Michele T. Pato, Nicholas G. Martin, Aiden Corvin, Michael Gill, René S. Kahn, Rolf Adolfsson, Josep Antoni Ramos-Quiroga, Frank Bellivier, Bruno Etain, Marion Leboyer, Thomas G. Schulze, Bernhard T. Baune, Ketil J. Oedegaard, Alessandro Serretti, Markus M. Nöthen, Elliot S. Gershon, Thomas Werge, Andrew M. McIntosh, Mikael Landén, Kari Stefansson, Bertram Müller-Myhsok, Michael Boehnke, Udo Dannlowski, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Patrick F. Sullivan, Ingrid Agartz, Ingrid Sigfrid Melle, Wade H. Berrettini, Vishwajit Nimgaonkar, Tõnu Esko, Andres Metspalu, Lisa A. Jones, Josep Antoni Ramos-Quiroga, Marta Ribasés, John Nurnberger, Naomi R. Wray, Arianna Di Florio, Michael C. O’Donovan, Howard J. Edenberg, Roel A. Ophoff, Laura J. Scott, Sven Cichon, Ole A. Andreassen, Pamela Sklar, John Kelsoe, Gerome Breen2017-08-08 (, , , ; similar)⁠:

Bipolar 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 881 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 achieved genome-wide statistical-significance including 20 novel loci. These statistically-significant loci contain genes encoding ion channels and neurotransmitter transporters (CACNA1C, GRIN2A, SCN2A, SLC4A1), synaptic components (RIMS1, ANK3), immune and energy metabolism components, and multiple potential therapeutic targets for mood stabilizer drugs.

Bipolar disorder type I (depressive and manic episodes; ~73% of our cases) is strongly genetically correlated with schizophrenia whereas type II (depressive and hypomanic episodes; ~17% of our cases) correlated more with major depression. Furthermore, bipolar disorder has a positive genetic correlation with educational attainment yet has no statistically-significant genetic correlation with intelligence.

These findings address key clinical questions and provide potential new biological mechanisms for bipolar disorder.