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 Scolnick, Sven Cichon, David St. Clair, Aiden Corvin, Hugh Gurling, Thomas Werge, Dan Rujescu, Douglas H.R. Blackwood, Carlos N. Pato, Anil K. MalhotraShaun Purcell, Frank Dudbridge, Benjamin M. Neale, Lizzy Rossin, Peter M. Visscher, Danielle Posthuma, Douglas M. Ruderfer, Ayman Fanous, Hreinn Stefansson, Stacy Steinberg, Bryan J. Mowry, Vera Golimbet, Marc De Hert, Erik G. Jönsson, István Bitter, Olli P.H. Pietiläinen, 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. Børglum, 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 Glenthøj, Stephanie Godard, Marian Hamshere, Mark Hansen, Thomas Hansen, Annette M. Hartmann, Frans A. Henskens, David M. Hougaard, Christina M. Hultman, Andrés Ingason, Assen V. Jablensky, Klaus D. Jakobsen, Maurice Jay, Gesche Jürgens, René S. 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 Lönnqvist, Carmel M. Loughland, Alan W. MacLean, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Pat Malloy, Manuel Mattheisen, Morten Mattingsdal, Kevin A. McGhee, John J. 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. Nöthen, Colm T. O'Dushlaine, Ann Olincy, Line Olsen, F. Anthony O'Neill, Torben F. Ørntoft, Michael J. Owen, Christos Pantelis, George 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, János M. Réthelyi, 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 Van Den Oord, Jim Van Os, Ruud Van Winkel, Jan Veldink, Dermot Walsh, August G. Wang, Durk Wiersma, Dieter B. Wildenauer, Hywel J. Williams, Nigel M. Williams, Brandon Wormley, Stan Zammit, Patrick F. Sullivan, Michael C. O'Donovan, Mark J. Daly, Pablo V. Gejman

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1304 Scopus citations

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 × 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 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9).

Original languageEnglish (US)
Pages (from-to)969-978
Number of pages10
JournalNature Genetics
Volume43
Issue number10
DOIs
StatePublished - Oct 2011

ASJC Scopus subject areas

  • Genetics

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