Genome-wide association study identifies five new schizophrenia loci

Stephan Ripke, Alan R. Sanders, Kenneth S. Kendler, Douglas F. Levinson, Pamela Sklar, Peter A. Holmans, Dan-Yu Lin, Jubao Duan, Roel A. Ophoff, Ole A. Andreassen, Edward M. Scolnick, Sven Cichon, David St. Clair, Aiden Corvin, Hugh Gurling, Thomas Werge, Dan Rujescu, Douglas H. R. Blackwood, Carlos N. Pato, Anil K. MalhotraShaun M. Purcell, Frank Dudbridge, Benjamin M. Neale, Lizzy Rossin, Peter M. Visscher, Danielle Posthuma, Douglas M. Ruderfer, Ayman H. Fanous, Hreinn Stefansson, Stacy Steinberg, Bryan J. Mowry, Vera Golimbet, Marc De Hert, Erik G. Jonsson, Istvan Bitter, Olli P. H. Pietilainen, David A. Collier, Sarah Tosato, Ingrid Agartz, Margot Albus, Madeline Alexander, Richard L. Amdur, Farooq Amin, Nicholas Bass, Sarah E. Bergen, Donald W. Black, Anders D. Borglum, Matthew A. Brown, Richard Bruggeman, Nancy G. Buccola, William F. Byerley, Wiepke Cahn, Rita M. Cantor, Vaughan J. Carr, Stanley V. Catts, Khalid Choudhury, C. Robert Cloninger, Paul Cormican, Nicholas Craddock, Patrick A. Danoy, Susmita Datta, Lieuwe de Haan, Ditte Demontis, Dimitris Dikeos, Srdjan Djurovic, Peter Donnelly, Gary Donohoe, Linh Duong, Sarah Dwyer, Anders Fink-Jensen, Robert Freedman, Nelson B. Freimer, Marion Friedl, Lyudmila Georgieva, Ina Giegling, Michael Gill, Birte Glenthoj, Stephanie Godard, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Annette M. Hartmann, Frans A. Henskens, David M. Hougaard, Christina M. Hultman, Andres Ingason, Assen V. Jablensky, Klaus D. Jakobsen, Maurice Jay, Gesche Juergens, Renes Kahn, Matthew C. Keller, Gunter Kenis, Elaine Kenny, Yunjung Kim, George K. Kirov, Heike Konnerth, Bettina Konte, Lydia Krabbendam, Robert Krasucki, Virginia K. Lasseter, Claudine Laurent, Jacob Lawrence, Todd Lencz, F. Bernard Lerer, Kung-Yee Liang, Paul Lichtenstein, Jeffrey A. Lieberman, Don H. Linszen, Jouko Lonnqvist, Carmel M. Loughland, Alan W. Maclean, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Pat Malloy, Manuel Mattheisen, Morten Mattingsdal, Kevin A. McGhee, John McGrath, Andrew McIntosh, Duncan E. McLean, Andrew McQuillin, Ingrid Melle, Patricia T. Michie, Vihra Milanova, Derek W. Morris, Ole Mors, Preben B. Mortensen, Valentina Moskvina, Pierandrea Muglia, Inez Myin-Germeys, Deborah A. Nertney, Gerald Nestadt, Jimmi Nielsen, Ivan Nikolov, Merete Nordentoft, Nadine Norton, Markus M. Noethen, Colm T. O'Dushlaine, Ann Olincy, Line Olsen, F. Anthony O'Neill, Torben F. Orntoft, Michael J. Owen, Christos Pantelis, George N. Papadimitriou, Michele T. Pato, Leena Peltonen, Hannes Petursson, Ben Pickard, Jonathan Pimm, Ann E. Pulver, Vinay Puri, Digby Quested, Emma M. Quinn, Henrik B. Rasmussen, Janos M. Rethelyi, Robert Ribble, Marcella Rietschel, Brien P. Riley, Mirella Ruggeri, Ulrich Schall, Thomas G. Schulze, Sibylle G. Schwab, Rodney J. Scott, Jianxin Shi, Engilbert Sigurdsson, Jeremy M. Silverman, Chris C. A. Spencer, Kari Stefansson, Amy Strange, Eric Strengman, T. Scott Stroup, Jaana Suvisaari, Lars Terenius, Srinivasa Thirumalai, Johan H. Thygesen, Sally Timm, Draga Toncheva, Edwin J. C. G. Van den Oord, Jim van Os, Ruud van Winkel, Jan H. Veldink, Dermot Walsh, August G. Wang, Durk Wiersma, Dieter B. Wildenauer, Hywel J. Williams, Nigel M. Williams, Brandon K. Wormley, Stan Zammit, Patrick F. Sullivan, Michael C. O'Donovan, Mark J. Daly, Pablo V. Gejman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).
Original languageEnglish
Pages (from-to)969-U77
JournalNature Genetics
Volume43
Issue number10
DOIs
Publication statusPublished - Oct 2011

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