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; Sang Hong Lee; Patrik K.E. Magnusson; Nick Sanchez; Eli A. Stahl; Stephanie Williams; Naomi R. Wray; Kai Xia; Francesco Bettella; Anders D. Borglum; 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

doi:10.1038/ng.2742

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, Sang Hong Lee, Patrik K.E. Magnusson, Nick Sanchez, Eli A. Stahl, Stephanie Williams, Naomi R. Wray, Kai Xia, Francesco Bettella, Anders D. BorglumBrendan 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1007 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1150-1159
Number of pages	10
Journal	Nature Genetics
Volume	45
Issue number	10
DOIs	https://doi.org/10.1038/ng.2742
Publication status	Published - Oct 2013

Bibliographical note

Funding Information:
We are deeply grateful for the participation of all subjects contributing to this research and to the collection team that worked to recruit them: E. Flordal-Thelander, A.-B. Holmgren, M. Hallin, M. Lundin, A.-K. Sundberg, C. Pettersson, R. Satgunanthan-Dawoud, S. Hassellund, M. Rådstrom, B. Ohlander, L. Nyrén and I. Kizling. Funding support was provided by the NIMH (R01 MH077139 to P.F.S. and R01 MH095034 to P.S.), the Stanley Center for Psychiatric Research, the Sylvan Herman Foundation, the Friedman Brain Institute at the Mount Sinai School of Medicine, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, the Swedish County Council, the Söderström Königska Foundation and the Netherlands Scientific Organization (NWO 645-000-003). SGENE was supported by European Union grant HEALTH-F2-2009-223423 (project PsychCNVs). The study of the Aarhus sample was supported by grants from the Danish Strategic Research Council, H. Lundbeck A/S, the Faculty of Health Sciences at Aarhus University, the Lundbeck Foundation and the Stanley Research Foundation. The Wellcome Trust Case Control Consortium 2 project collection was funded by the Wellcome Trust (085475/B/08/Z and 085475/Z/08/Z). The funders had no role in study design, execution or analysis or in manuscript preparation.

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10.1038/ng.2742

Cite this

Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., Collins, A. L., Crowley, J. J., Fromer, M., Kim, Y., Lee, S. H., Magnusson, P. K. E., Sanchez, N., Stahl, E. A., Williams, S., Wray, N. R., Xia, K., Bettella, F., ... 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

@article{52cf32101f9944ed9140240a25d84982,

title = "Genome-wide association analysis identifies 13 new risk loci for schizophrenia",

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.",

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

note = "Funding Information: We are deeply grateful for the participation of all subjects contributing to this research and to the collection team that worked to recruit them: E. Flordal-Thelander, A.-B. Holmgren, M. Hallin, M. Lundin, A.-K. Sundberg, C. Pettersson, R. Satgunanthan-Dawoud, S. Hassellund, M. R{\aa}dstrom, B. Ohlander, L. Nyr{\'e}n and I. Kizling. Funding support was provided by the NIMH (R01 MH077139 to P.F.S. and R01 MH095034 to P.S.), the Stanley Center for Psychiatric Research, the Sylvan Herman Foundation, the Friedman Brain Institute at the Mount Sinai School of Medicine, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, the Swedish County Council, the S{\"o}derstr{\"o}m K{\"o}nigska Foundation and the Netherlands Scientific Organization (NWO 645-000-003). SGENE was supported by European Union grant HEALTH-F2-2009-223423 (project PsychCNVs). The study of the Aarhus sample was supported by grants from the Danish Strategic Research Council, H. Lundbeck A/S, the Faculty of Health Sciences at Aarhus University, the Lundbeck Foundation and the Stanley Research Foundation. The Wellcome Trust Case Control Consortium 2 project collection was funded by the Wellcome Trust (085475/B/08/Z and 085475/Z/08/Z). The funders had no role in study design, execution or analysis or in manuscript preparation.",

year = "2013",

month = oct,

doi = "10.1038/ng.2742",

language = "English",

volume = "45",

pages = "1150--1159",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Ripke, S, O'Dushlaine, C, Chambert, K, Moran, JL, Kähler, AK, Akterin, S, Bergen, SE, Collins, AL, Crowley, JJ, Fromer, M, Kim, Y, Lee, SH, Magnusson, PKE, Sanchez, N, Stahl, EA, Williams, S, Wray, NR, Xia, K, Bettella, F, Borglum, AD, Bulik-Sullivan, BK, Cormican, P, Craddock, N, De Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, ML, Holmans, P, Hougaard, DM, Kendler, KS, Lin, K, Morris, DW, Mors, O, Mortensen, PB, Neale, BM, O'Neill, FA, Owen, MJ, Milovancevic, MP, Posthuma, D, Powell, J, Richards, AL, Riley, BP, Ruderfer, D, Sigurdsson, E, Silagadze, T, Smit, AB, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, JT, Levinson, DF, Gejman, PV, Laurent, C, Mowry, BJ, O'Donovan, MC, Pulver, AE, Schwab, SG, Wildenauer, DB, Dudbridge, F, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, FB, Liang, KY, Maier, W, Mallet, J, Nertney, DA, Nestadt, G, Norton, N, Papadimitriou, GN, Ribble, R, Sanders, AR, Silverman, JM, Walsh, D, Williams, NM, Wormley, B, Arranz, MJ, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo-Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, RS, Kalaydjieva, L, Lawrie, S, Lewis, CM, Linszen, DH, Mata, I, McIntosh, A, Murray, RM, Ophoff, RA, Rujescu, D, Van Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Donnelly, P, Blackwell, JM, Brown, MA, Casas, JP, Corvin, AP, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, RD, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Tashakkori-Ghanbaria, A, Waller, MJ, Weston, P, Widaa, S, Whittaker, P, Barroso, I, Deloukas, P, McCarthy, MI, Stefansson, K, Scolnick, E, Purcell, S, McCarroll, SA, Sklar, P, Hultman, CM & Sullivan, PF 2013, 'Genome-wide association analysis identifies 13 new risk loci for schizophrenia', Nature Genetics, vol. 45, no. 10, pp. 1150-1159. https://doi.org/10.1038/ng.2742

TY - JOUR

T1 - Genome-wide association analysis identifies 13 new risk loci for schizophrenia

AU - Ripke, Stephan

AU - O'Dushlaine, Colm

AU - Chambert, Kimberly

AU - Moran, Jennifer L.

AU - Kähler, Anna K.

AU - Akterin, Susanne

AU - Bergen, Sarah E.

AU - Collins, Ann L.

AU - Crowley, James J.

AU - Fromer, Menachem

AU - Kim, Yunjung

AU - Lee, Sang Hong

AU - Magnusson, Patrik K.E.

AU - Sanchez, Nick

AU - Stahl, Eli A.

AU - Williams, Stephanie

AU - Wray, Naomi R.

AU - Xia, Kai

AU - Bettella, Francesco

AU - Borglum, Anders D.

AU - Bulik-Sullivan, Brendan K.

AU - Cormican, Paul

AU - Craddock, Nick

AU - De Leeuw, Christiaan

AU - Durmishi, Naser

AU - Gill, Michael

AU - Golimbet, Vera

AU - Hamshere, Marian L.

AU - Holmans, Peter

AU - Hougaard, David M.

AU - Kendler, Kenneth S.

AU - Lin, Kuang

AU - Morris, Derek W.

AU - Mors, Ole

AU - Mortensen, Preben B.

AU - Neale, Benjamin M.

AU - O'Neill, Francis A.

AU - Owen, Michael J.

AU - Milovancevic, Milica Pejovic

AU - Posthuma, Danielle

AU - Powell, John

AU - Richards, Alexander L.

AU - Riley, Brien P.

AU - Ruderfer, Douglas

AU - Sigurdsson, Engilbert

AU - Silagadze, Teimuraz

AU - Smit, August B.

AU - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Suvisaari, Jaana

AU - Tosato, Sarah

AU - Verhage, Matthijs

AU - Walters, James T.

AU - Levinson, Douglas F.

AU - Gejman, Pablo V.

AU - Laurent, Claudine

AU - Mowry, Bryan J.

AU - O'Donovan, Michael C.

AU - Pulver, Ann E.

AU - Schwab, Sibylle G.

AU - Wildenauer, Dieter B.

AU - Dudbridge, Frank

AU - Shi, Jianxin

AU - Albus, Margot

AU - Alexander, Madeline

AU - Campion, Dominique

AU - Cohen, David

AU - Dikeos, Dimitris

AU - Duan, Jubao

AU - Eichhammer, Peter

AU - Godard, Stephanie

AU - Hansen, Mark

AU - Lerer, F. Bernard

AU - Liang, Kung Yee

AU - Maier, Wolfgang

AU - Mallet, Jacques

AU - Nertney, Deborah A.

AU - Nestadt, Gerald

AU - Norton, Nadine

AU - Papadimitriou, George N.

AU - Ribble, Robert

AU - Sanders, Alan R.

AU - Silverman, Jeremy M.

AU - Walsh, Dermot

AU - Williams, Nigel M.

AU - Wormley, Brandon

AU - Arranz, Maria J.

AU - Bakker, Steven

AU - Bender, Stephan

AU - Bramon, Elvira

AU - Collier, David

AU - Crespo-Facorro, Benedicto

AU - Hall, Jeremy

AU - Iyegbe, Conrad

AU - Jablensky, Assen

AU - Kahn, Rene S.

AU - Kalaydjieva, Luba

AU - Lawrie, Stephen

AU - Lewis, Cathryn M.

AU - Linszen, Don H.

AU - Mata, Ignacio

AU - McIntosh, Andrew

AU - Murray, Robin M.

AU - Ophoff, Roel A.

AU - Rujescu, Dan

AU - Van Os, Jim

AU - Walshe, Muriel

AU - Weisbrod, Matthias

AU - Wiersma, Durk

AU - Donnelly, Peter

AU - Blackwell, Jenefer M.

AU - Brown, Matthew A.

AU - Casas, Juan P.

AU - Corvin, Aiden P.

AU - Duncanson, Audrey

AU - Jankowski, Janusz

AU - Markus, Hugh S.

AU - Mathew, Christopher G.

AU - Palmer, Colin N.A.

AU - Plomin, Robert

AU - Rautanen, Anna

AU - Sawcer, Stephen J.

AU - Trembath, Richard C.

AU - Viswanathan, Ananth C.

AU - Wood, Nicholas W.

AU - Spencer, Chris C.A.

AU - Band, Gavin

AU - Bellenguez, Céline

AU - Freeman, Colin

AU - Hellenthal, Garrett

AU - Giannoulatou, Eleni

AU - Pirinen, Matti

AU - Pearson, Richard D.

AU - Strange, Amy

AU - Su, Zhan

AU - Vukcevic, Damjan

AU - Langford, Cordelia

AU - Hunt, Sarah E.

AU - Edkins, Sarah

AU - Gwilliam, Rhian

AU - Blackburn, Hannah

AU - Bumpstead, Suzannah J.

AU - Dronov, Serge

AU - Gillman, Matthew

AU - Gray, Emma

AU - Hammond, Naomi

AU - Jayakumar, Alagurevathi

AU - McCann, Owen T.

AU - Liddle, Jennifer

AU - Potter, Simon C.

AU - Ravindrarajah, Radhi

AU - Ricketts, Michelle

AU - Tashakkori-Ghanbaria, Avazeh

AU - Waller, Matthew J.

AU - Weston, Paul

AU - Widaa, Sara

AU - Whittaker, Pamela

AU - Barroso, Ines

AU - Deloukas, Panos

AU - McCarthy, Mark I.

AU - Stefansson, Kari

AU - Scolnick, Edward

AU - Purcell, Shaun

AU - McCarroll, Steven A.

AU - Sklar, Pamela

AU - Hultman, Christina M.

AU - Sullivan, Patrick F.

N1 - Funding Information: We are deeply grateful for the participation of all subjects contributing to this research and to the collection team that worked to recruit them: E. Flordal-Thelander, A.-B. Holmgren, M. Hallin, M. Lundin, A.-K. Sundberg, C. Pettersson, R. Satgunanthan-Dawoud, S. Hassellund, M. Rådstrom, B. Ohlander, L. Nyrén and I. Kizling. Funding support was provided by the NIMH (R01 MH077139 to P.F.S. and R01 MH095034 to P.S.), the Stanley Center for Psychiatric Research, the Sylvan Herman Foundation, the Friedman Brain Institute at the Mount Sinai School of Medicine, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, the Swedish County Council, the Söderström Königska Foundation and the Netherlands Scientific Organization (NWO 645-000-003). SGENE was supported by European Union grant HEALTH-F2-2009-223423 (project PsychCNVs). The study of the Aarhus sample was supported by grants from the Danish Strategic Research Council, H. Lundbeck A/S, the Faculty of Health Sciences at Aarhus University, the Lundbeck Foundation and the Stanley Research Foundation. The Wellcome Trust Case Control Consortium 2 project collection was funded by the Wellcome Trust (085475/B/08/Z and 085475/Z/08/Z). The funders had no role in study design, execution or analysis or in manuscript preparation.

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84885020424&partnerID=8YFLogxK

U2 - 10.1038/ng.2742

DO - 10.1038/ng.2742

M3 - Article

C2 - 23974872

AN - SCOPUS:84885020424

SN - 1061-4036

VL - 45

SP - 1150

EP - 1159

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

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