Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Stephan Ripke, Colm O'Dushlaine, Kimberly Chambert, Jennifer L. Moran, Anna K. Kähler, Susanne Akterin, Sarah E. Bergen, Ann L. Collins, James J. Crowley, Menachem Fromer, Yunjung Kim, Hong Lee, Patrik K.E. Magnusson, Nick Sanchez, Eli A. Stahl, Stephanie Williams, Naomi R. Wray, Kai Xia, Francesco Bettella, Anders D. Borglum & 147 others Brendan K. Bulik-Sullivan, Paul Cormican, Nick Craddock, Christiaan De Leeuw, Naser Durmishi, Michael Gill, Vera Golimbet, Marian L. Hamshere, Peter Holmans, David M. Hougaard, Kenneth S. Kendler, Kuang Lin, Derek W. Morris, Ole Mors, Preben B. Mortensen, Benjamin M. Neale, Francis A. O'Neill, Michael J. Owen, Milica Pejovic Milovancevic, Danielle Posthuma, John Powell, Alexander L. Richards, Brien P. Riley, Douglas Ruderfer, Engilbert Sigurdsson, Teimuraz Silagadze, August B. Smit, Hreinn Stefansson, Stacy Steinberg, Jaana Suvisaari, Sarah Tosato, Matthijs Verhage, James T. Walters, Douglas F. Levinson, Pablo V. Gejman, Claudine Laurent, Bryan J. Mowry, Michael C. O'Donovan, Ann E. Pulver, Sibylle G. Schwab, Dieter B. Wildenauer, Frank Dudbridge, Jianxin Shi, Margot Albus, Madeline Alexander, Dominique Campion, David Cohen, Dimitris Dikeos, Jubao Duan, Peter Eichhammer, Stephanie Godard, Mark Hansen, F. Bernard Lerer, Kung Yee Liang, Wolfgang Maier, Jacques Mallet, Deborah A. Nertney, Gerald Nestadt, Nadine Norton, George N. Papadimitriou, Robert Ribble, Alan R. Sanders, Jeremy M. Silverman, Dermot Walsh, Nigel M. Williams, Brandon Wormley, Maria J. Arranz, Steven Bakker, Stephan Bender, Elvira Bramon, David Collier, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Assen Jablensky, Rene S. Kahn, Luba Kalaydjieva, Stephen Lawrie, Cathryn M. Lewis, Don H. Linszen, Ignacio Mata, Andrew McIntosh, Robin M. Murray, Roel A. Ophoff, Dan Rujescu, Jim Van Os, Muriel Walshe, Matthias Weisbrod, Durk Wiersma, Peter Donnelly, Jenefer M. Blackwell, Matthew A. Brown, Juan P. Casas, Aiden P. Corvin, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Chris C.A. Spencer, Gavin Band, Céline Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard D. Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Sarah E. Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T. McCann, Jennifer Liddle, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Avazeh Tashakkori-Ghanbaria, Matthew J. Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Ines Barroso, Panos Deloukas, Mark I. McCarthy, Kari Stefansson, Edward Scolnick, Shaun Purcell, Steven A. McCarroll, Pamela Sklar, Christina M. Hultman, Patrick F. Sullivan

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Abstract

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

LanguageEnglish
Pages1150-1159
Number of pages10
JournalNature Genetics
Volume45
Issue number10
DOIs
Publication statusPublished - 1 Oct 2013

ASJC Scopus subject areas

  • Genetics

Cite this

Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., ... Sullivan, P. F. (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45(10), 1150-1159. https://doi.org/10.1038/ng.2742