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Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Parikshak, Neelroop N, Newhouse, Stephen, Ripke, Stephan, Neale, Benjamin M, Purcell, Shaun M, Posthuma, Danielle, Nurnberger, John I, Lee, S Hong, Faraone, Stephen V, Perlis, Roy H, Mowry, Bryan J, Thapar, Anita, Goddard, Michael E, Witte, John S, Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole A, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan E, Asherson, Philip, Azevedo, Maria H, Backlund, Lena, Badner, Judith A, Bailey, Anthony J, Banaschewski, Tobias, Barchas, Jack D, Barnes, Michael R, Barrett, Thomas B, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayés, Mònica, Bellivier, Frank, Bergen, Sarah E, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth B, Black, Donald W, Blackwood, Douglas H R, Bloss, Cinnamon S, Boehnke, Michael, Boomsma, Dorret I, Breuer, René, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy G, Buitelaar, Jan K, Bunney, William E, Buxbaum, Joseph D, Byerley, William F, Byrne, Enda M, Caesar, Sian, Cahn, Wiepke, Cantor, Rita M, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Mattheisen, Manuel, Cloninger, C Robert, Collier, David A, Cook, Edwin H, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William H, Craig, David W, Craig, Ian W, Crosbie, Jennifer, Cuccaro, Michael L, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco J, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary J, Doyle, Alysa E, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard P, Edenberg, Howard J, Elia, Josephine, Ennis, Sean, Etain, Bruno, Fanous, Ayman, Farmer, Anne E, Ferrier, I Nicol, Flickinger, Matthew, Fombonne, Eric, Foroud, Tatiana, Frank, Josef, Franke, Barbara, Fraser, Christine, Freedman, Robert, Freimer, Nelson B, Freitag, Christine M, Friedl, Marion, Frisén, Louise, Gallagher, Louise, Gejman, Pablo V, Georgieva, Lyudmila, Gershon, Elliot S, Giegling, Ina, Gill, Michael, Gordon, Scott D, Gordon-Smith, Katherine, Green, Elaine K, Greenwood, Tiffany A, Grice, Dorothy E, Gross, Magdalena, Grozeva, Detelina, Guan, Weihua, Gurling, Hugh, De Haan, Lieuwe, Haines, Jonathan L, Hakonarson, Hakon, Hallmayer, Joachim, Hamilton, Steven P, Hamshere, Marian Lindsay, Hansen, Thomas F, Hartmann, Annette M, Hautzinger, Martin, Heath, Andrew C, Henders, Anjali K, Herms, Stefan, Hickie, Ian B, Hipolito, Maria, Hoefels, Susanne, Holsboer, Florian, Hoogendijk, Witte J, Hottenga, Jouke-Jan, Hultman, Christina M, Hus, Vanessa, Ingason, Andrés, Ising, Marcus, Jamain, Stéphane, Jones, Edward G, Jones, Ian Richard, Jones, Lisa, Tzeng, Jung-Ying, Kähler, Anna K, Kahn, René S, Kandaswamy, Radhika, Keller, Matthew C, Kennedy, James L, Kenny, Elaine, Kent, Lindsey, Kim, Yunjung, Kirov, George, Klauck, Sabine M, Klei, Lambertus, Knowles, James A, Kohli, Martin A, Koller, Daniel L, Konte, Bettina, Korszun, Ania, Krabbendam, Lydia, Krasucki, Robert, Kuntsi, Jonna, Kwan, Phoenix, Landén, Mikael, Längström, Niklas, Lathrop, Mark, Lawrence, Jacob, Lawson, William B, Leboyer, Marion, Ledbetter, David H, Lencz, Todd, Lesch, Klaus-Peter, Levinson, Douglas F, Lewis, Cathryn M, Li, Jun, Lichtenstein, Paul, Lieberman, Jeffrey A, Lin, Dan-Yu, Linszen, Don H, Liu, Chunyu, Lohoff, Falk W, Loo, Sandra K, Lord, Catherine, Lowe, Jennifer K, Lucae, Susanne, MacIntyre, Donald J, Madden, Pamela A F, Maestrini, Elena, Magnusson, Patrik K E, Mahon, Pamela B, Maier, Wolfgang, Malhotra, Anil K, Mane, Shrikant M, Martin, Christa L, Martin, Nicholas G, Matthews, Keith, Mattingsdal, Morten, McCarroll, Steven A, McGhee, Kevin A, McGough, James J, McGrath, Patrick J, McGuffin, Peter, McInnis, Melvin G, McIntosh, Andrew, McKinney, Rebecca, McLean, Alan W, McMahon, Francis J, McMahon, William M, McQuillin, Andrew, Medeiros, Helena, Medland, Sarah E, Meier, Sandra, Melle, Ingrid, Meng, Fan, Meyer, Jobst, Middeldorp, Christel M, Middleton, Lefkos, Milanova, Vihra, Miranda, Ana, Monaco, Anthony P, Montgomery, Grant W, Moran, Jennifer L, Moreno-De-Luca, Daniel, Morken, Gunnar, Morris, Derek W, Morrow, Eric M, Escott-Price, Valentina, Muglia, Pierandrea, Mühleisen, Thomas W, Muir, Walter J, Müller-Myhsok, Bertram, Murtha, Michael, Myers, Richard M, Myin-Germeys, Inez, Neale, Michael C, Nelson, Stan F, Nievergelt, Caroline M, Nikolov, Ivan, Nimgaonkar, Vishwajit, Nolen, Willem A, Nöthen, Markus M, Nwulia, Evaristus A, Nyholt, Dale R, Oades, Robert D, Olincy, Ann, Oliveira, Guiomar, Olsen, Line, Ophoff, Roel A, Osby, Urban, Owen, Michael John, Palotie, Aarno, Parr, Jeremy R, Paterson, Andrew D, Pato, Carlos N, Pato, Michele T, Penninx, Brenda W, Pergadia, Michele L, Pericak-Vance, Margaret A, Pickard, Benjamin S, Pimm, Jonathan, Piven, Joseph, Potash, James B, Poustka, Fritz, Propping, Peter, Puri, Vinay, Quested, Digby J, Quinn, Emma M, Ramos-Quiroga, Josep Antoni, Rasmussen, Henrik B, Raychaudhuri, Soumya, Rehnström, Karola, Reif, Andreas, Ribasés, Marta, Rice, John P, Rietschel, Marcella, Roeder, Kathryn, Roeyers, Herbert, Rothenberger, Aribert, Rouleau, Guy, Ruderfer, Douglas, Rujescu, Dan, Sanders, Alan R, Sanders, Stephan J, Santangelo, Susan L, Sergeant, Joseph A, Schachar, Russell, Schalling, Martin, Schatzberg, Alan F, Scheftner, William A, Schellenberg, Gerard D, Scherer, Stephen W, Schork, Nicholas J, Schulze, Thomas G, Schumacher, Johannes, Schwarz, Markus, Scolnick, Edward, Scott, Laura J, Shi, Jianxin, Shilling, Paul D, Shyn, Stanley I, Silverman, Jeremy M, Slager, Susan L, Smalley, Susan L, Smit, Johannes H, Smith, Erin N, Sonuga-Barke, Edmund J S, Clair, David St., State, Matthew, Steffens, Michael, Steinhausen, Hans-Christoph, Strauss, John S, Strohmaier, Jana, Stroup, T Scott, Sutcliffe, James S, Szatmari, Peter, Szelinger, Szabocls, Thirumalai, Srinivasa, Thompson, Robert C, Todorov, Alexandre A, Tozzi, Federica, Treutlein, Jens, Uhr, Manfred, van den Oord, Edwin J C G, Van Grootheest, Gerard, Van Os, Jim, Vicente, Astrid M, Vieland, Veronica J, Vincent, John B, Visscher, Peter M, Walsh, Christopher A, Wassink, Thomas H, Watson, Stanley J, Weissman, Myrna M, Werge, Thomas, Wienker, Thomas F, Wijsman, Ellen M, Willemsen, Gonneke, Williams, Nigel, Willsey, A Jeremy, Witt, Stephanie H, Xu, Wei, Young, Allan H, Yu, Timothy W, Zammit, Stanley, Zandi, Peter P, Zhang, Peng, Zitman, Frans G, Zöllner, Sebastian, Devlin, Bernie, Kelsoe, John R, Sklar, Pamela, Daly, Mark J, O'Donovan, Michael Conlon, Craddock, Nicholas John, Kendler, Kenneth S, A Weiss, Lauren, Wray, Naomi R, Zhao, Zhaoming, Geschwind, Daniel H, Sullivan, Patrick F, Smoller, Jordan W, Holmans, Peter Alan and Breen, Gerome 2015. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nature Neuroscience 18 (2) , pp. 199-209. 10.1038/nn.3922

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Abstract

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Nature Publishing Group
ISSN: 1097-6256
Last Modified: 10 Oct 2017 16:27
URI: http://orca-mwe.cf.ac.uk/id/eprint/74732

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