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

S. Ripke; C. O'Dushlaine; K. Chambert; J.L. Moran; A.K. Kähler; S. Akterin; S.E. Bergen; A.L. Collins; J.J. Crowley; M. Fromer; Y. Kim; S.H. Lee; P.K. Magnusson; N. Sanchez; E.A. Stahl; S. Williams; N.R. Wray; K. Xia; F. Bettella; A. D. Borglum; B.K. Bulik-Sullivan; P. Cormican; N. Craddock; C.A. de Leeuw; N. Durmishi; M. Gill; V. Golimbet; M.L. Hamshere; P. Holmans; D. M. Hougaard; K.S. Kendler; K. Lin; D. W. Morris; O. Mors; P.B. Mortensen; B. M. Neale; F. A. O'Neill; M.J. Owen; M.P. Milovancevic; D. Posthuma; J. Powell; A.L. Richards; B.P. Riley; D. Ruderfer; D. Rujescu; E. Sigurdsson; T. Silagadze; A.B. Smit; H. Stefansson; S. Steinberg; J. Suvisaari; S. Tosato; M. Verhage; T.J. Walters; D.F. Levinson; P.V. Gejman; C. Laurent; B. J. Mowry; M.C. O'Donovan; A. E. Pulver; S.G. Schwab; D. B. Wildenauer; F. Dudbridge; J. Shi; M. Albus; M. Alexander; D. Campion; D. Cohen; D. Dikeos; J. Duan; P. Eichhammer; S. Godard; M. Hansen; F.B. Lerer; K.Y. Liang; W. Maier; J. Mallet; D. A. Nertney; G. Nestadt; N. Norton; F.A. O'Neill; G.N. Papadimitriou; R. Ribble; A.R. Sanders; J.M. Silverman; B. Wormley; M.J. Arranz; S. Bakker; S. Bender; E. Bramon; D. Collier; B. Crespo-Facorro; J. Hall; C. Iyegbe; A. Jablensky; R.S. Kahn; L. Kalaydjieva; S.M. Lawrie; C.M. Lewis; D.H. Linszen; I. Mata; A. McIntosh; R.M. Murray; R.A. Ophoff; J. van Os; M. Walshe; M. Weisbrod; D. Wiersma; P. Donnely; I. Barasso; J.M. Blackwell; M.A. Brown; J.P. Casas; A.P. Corvin; P. Deloukas; A. Duncanson; J. Jankowski; H.S. Markus; C.G. Mathew; C.N. Palmer; R. Plomin; A. Rautanen; S.J. Sawcer; R.C. Trembath; A.C. Viswanathan; N.W. Wood; C. C. Spencer; G. Band; C. Bellenguez; C. Freeman; G. Hellenthal; E. Giannoulatou; M. Pirinen; R.D. Pearson; A. Strange; Z. Su; D. Vukcevic; C. Langford; S.E. Hunt; S. Edkins; R. Gwilliam; H. Blackburn; S. Bumpstead; S. Dronov; M. Gillman; E. Gray; N. Hammond; A. Jayakumar; O.T. McCann; J. Liddle; S.C. Potter; R. Ravindrarajah; M. Ricketts; A. Tashakkori-Ghanbaria; M.J. Waller; P. Weston; S. Widaa; P. Whittaker; I. Barrroso; M.I. McCarthy; C.C. Spencer; K. Stefansson; E. Scolnick; S. Purcell; S.A. McCarroll; P. Sklar; C. M. Hultman; P.F. Sullivan

doi:10.1038/ng.2742

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

S. Ripke, C. O'Dushlaine, K. Chambert, J.L. Moran, A.K. Kähler, S. Akterin, S.E. Bergen, A.L. Collins, J.J. Crowley, M. Fromer, Y. Kim, S.H. Lee, P.K. Magnusson, N. Sanchez, E.A. Stahl, S. Williams, N.R. Wray, K. Xia, F. Bettella, A. D. BorglumB.K. Bulik-Sullivan, P. Cormican, N. Craddock, C.A. de Leeuw, N. Durmishi, M. Gill, V. Golimbet, M.L. Hamshere, P. Holmans, D. M. Hougaard, K.S. Kendler, K. Lin, D. W. Morris, O. Mors, P.B. Mortensen, B. M. Neale, F. A. O'Neill, M.J. Owen, M.P. Milovancevic, D. Posthuma, J. Powell, A.L. Richards, B.P. Riley, D. Ruderfer, D. Rujescu, E. Sigurdsson, T. Silagadze, A.B. Smit, H. Stefansson, S. Steinberg, J. Suvisaari, S. Tosato, M. Verhage, T.J. Walters, D.F. Levinson, P.V. Gejman, C. Laurent, B. J. Mowry, M.C. O'Donovan, A. E. Pulver, S.G. Schwab, D. B. Wildenauer, F. Dudbridge, J. Shi, M. Albus, M. Alexander, D. Campion, D. Cohen, D. Dikeos, J. Duan, P. Eichhammer, S. Godard, M. Hansen, F.B. Lerer, K.Y. Liang, W. Maier, J. Mallet, D. A. Nertney, G. Nestadt, N. Norton, F.A. O'Neill, G.N. Papadimitriou, R. Ribble, A.R. Sanders, J.M. Silverman, B. Wormley, M.J. Arranz, S. Bakker, S. Bender, E. Bramon, D. Collier, B. Crespo-Facorro, J. Hall, C. Iyegbe, A. Jablensky, R.S. Kahn, L. Kalaydjieva, S.M. Lawrie, C.M. Lewis, D.H. Linszen, I. Mata, A. McIntosh, R.M. Murray, R.A. Ophoff, J. van Os, M. Walshe, M. Weisbrod, D. Wiersma, P. Donnely, I. Barasso, J.M. Blackwell, M.A. Brown, J.P. Casas, A.P. Corvin, P. Deloukas, A. Duncanson, J. Jankowski, H.S. Markus, C.G. Mathew, C.N. Palmer, R. Plomin, A. Rautanen, S.J. Sawcer, R.C. Trembath, A.C. Viswanathan, N.W. Wood, C. C. Spencer, G. Band, C. Bellenguez, C. Freeman, G. Hellenthal, E. Giannoulatou, M. Pirinen, R.D. Pearson, A. Strange, Z. Su, D. Vukcevic, C. Langford, S.E. Hunt, S. Edkins, R. Gwilliam, H. Blackburn, S. Bumpstead, S. Dronov, M. Gillman, E. Gray, N. Hammond, A. Jayakumar, O.T. McCann, J. Liddle, S.C. Potter, R. Ravindrarajah, M. Ricketts, A. Tashakkori-Ghanbaria, M.J. Waller, P. Weston, S. Widaa, P. Whittaker, I. Barrroso, M.I. McCarthy, C.C. Spencer, K. Stefansson, E. Scolnick, S. Purcell, S.A. McCarroll, P. Sklar, C. M. Hultman, P.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. © 2013 Nature America, Inc. All rights reserved.

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

Bibliographical note

Multicenter Genetic Studies of Schizophrenia Consortium;Psychosis Endophenotypes International Consort; Wellcome Trust Case Control Consortium 2

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10.1038/ng.2742

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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., 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{6b6dbab0594346a4acf110e6003c769a,

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. {\textcopyright} 2013 Nature America, Inc. All rights reserved.",

author = "S. Ripke and C. O'Dushlaine and K. Chambert and J.L. Moran and A.K. K{\"a}hler and S. Akterin and S.E. Bergen and A.L. Collins and J.J. Crowley and M. Fromer and Y. Kim and S.H. Lee and P.K. Magnusson and N. Sanchez and E.A. Stahl and S. Williams and N.R. Wray and K. Xia and F. Bettella and Borglum, {A. D.} and B.K. Bulik-Sullivan and P. Cormican and N. Craddock and {de Leeuw}, C.A. and N. Durmishi and M. Gill and V. Golimbet and M.L. Hamshere and P. Holmans and Hougaard, {D. M.} and K.S. Kendler and K. Lin and Morris, {D. W.} and O. Mors and P.B. Mortensen and Neale, {B. M.} and O'Neill, {F. A.} and M.J. Owen and M.P. Milovancevic and D. Posthuma and J. Powell and A.L. Richards and B.P. Riley and D. Ruderfer and D. Rujescu and E. Sigurdsson and T. Silagadze and A.B. Smit and H. Stefansson and S. Steinberg and J. Suvisaari and S. Tosato and M. Verhage and T.J. Walters and D.F. Levinson and P.V. Gejman and C. Laurent and Mowry, {B. J.} and M.C. O'Donovan and Pulver, {A. E.} and S.G. Schwab and Wildenauer, {D. B.} and F. Dudbridge and J. Shi and M. Albus and M. Alexander and D. Campion and D. Cohen and D. Dikeos and J. Duan and P. Eichhammer and S. Godard and M. Hansen and F.B. Lerer and K.Y. Liang and W. Maier and J. Mallet and Nertney, {D. A.} and G. Nestadt and N. Norton and F.A. O'Neill and G.N. Papadimitriou and R. Ribble and A.R. Sanders and J.M. Silverman and B. Wormley and M.J. Arranz and S. Bakker and S. Bender and E. Bramon and D. Collier and B. Crespo-Facorro and J. Hall and C. Iyegbe and A. Jablensky and R.S. Kahn and L. Kalaydjieva and S.M. Lawrie and C.M. Lewis and D.H. Linszen and I. Mata and A. McIntosh and R.M. Murray and R.A. Ophoff and {van Os}, J. and M. Walshe and M. Weisbrod and D. Wiersma and P. Donnely and I. Barasso and J.M. Blackwell and M.A. Brown and J.P. Casas and A.P. Corvin and P. Deloukas and A. Duncanson and J. Jankowski and H.S. Markus and C.G. Mathew and C.N. Palmer and R. Plomin and A. Rautanen and S.J. Sawcer and R.C. Trembath and A.C. Viswanathan and N.W. Wood and Spencer, {C. C.} and G. Band and C. Bellenguez and C. Freeman and G. Hellenthal and E. Giannoulatou and M. Pirinen and R.D. Pearson and A. Strange and Z. Su and D. Vukcevic and C. Langford and S.E. Hunt and S. Edkins and R. Gwilliam and H. Blackburn and S. Bumpstead and S. Dronov and M. Gillman and E. Gray and N. Hammond and A. Jayakumar and O.T. McCann and J. Liddle and S.C. Potter and R. Ravindrarajah and M. Ricketts and A. Tashakkori-Ghanbaria and M.J. Waller and P. Weston and S. Widaa and P. Whittaker and I. Barrroso and M.I. McCarthy and C.C. Spencer and K. Stefansson and E. Scolnick and S. Purcell and S.A. McCarroll and P. Sklar and Hultman, {C. M.} and P.F. Sullivan",

note = "Multicenter Genetic Studies of Schizophrenia Consortium;Psychosis Endophenotypes International Consort; Wellcome Trust Case Control Consortium 2",

year = "2013",

doi = "10.1038/ng.2742",

language = "English",

volume = "45",

pages = "1150--1159",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

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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, PK, Sanchez, N, Stahl, EA, Williams, S, Wray, NR, Xia, K, Bettella, F, Borglum, AD, Bulik-Sullivan, BK, Cormican, P, Craddock, N, de Leeuw, CA, 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, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, AB, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, TJ, 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, O'Neill, FA, Papadimitriou, GN, Ribble, R, Sanders, AR, Silverman, JM, 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, SM, Lewis, CM, Linszen, DH, Mata, I, McIntosh, A, Murray, RM, Ophoff, RA, van Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Donnely, P, Barasso, I, Blackwell, JM, Brown, MA, Casas, JP, Corvin, AP, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CN, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CC, 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, S, 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, Barrroso, I, McCarthy, MI, Spencer, CC, 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, S.

AU - O'Dushlaine, C.

AU - Chambert, K.

AU - Moran, J.L.

AU - Kähler, A.K.

AU - Akterin, S.

AU - Bergen, S.E.

AU - Collins, A.L.

AU - Crowley, J.J.

AU - Fromer, M.

AU - Kim, Y.

AU - Lee, S.H.

AU - Magnusson, P.K.

AU - Sanchez, N.

AU - Stahl, E.A.

AU - Williams, S.

AU - Wray, N.R.

AU - Xia, K.

AU - Bettella, F.

AU - Borglum, A. D.

AU - Bulik-Sullivan, B.K.

AU - Cormican, P.

AU - Craddock, N.

AU - de Leeuw, C.A.

AU - Durmishi, N.

AU - Gill, M.

AU - Golimbet, V.

AU - Hamshere, M.L.

AU - Holmans, P.

AU - Hougaard, D. M.

AU - Kendler, K.S.

AU - Lin, K.

AU - Morris, D. W.

AU - Mors, O.

AU - Mortensen, P.B.

AU - Neale, B. M.

AU - O'Neill, F. A.

AU - Owen, M.J.

AU - Milovancevic, M.P.

AU - Posthuma, D.

AU - Powell, J.

AU - Richards, A.L.

AU - Riley, B.P.

AU - Ruderfer, D.

AU - Rujescu, D.

AU - Sigurdsson, E.

AU - Silagadze, T.

AU - Smit, A.B.

AU - Stefansson, H.

AU - Steinberg, S.

AU - Suvisaari, J.

AU - Tosato, S.

AU - Verhage, M.

AU - Walters, T.J.

AU - Levinson, D.F.

AU - Gejman, P.V.

AU - Laurent, C.

AU - Mowry, B. J.

AU - O'Donovan, M.C.

AU - Pulver, A. E.

AU - Schwab, S.G.

AU - Wildenauer, D. B.

AU - Dudbridge, F.

AU - Shi, J.

AU - Albus, M.

AU - Alexander, M.

AU - Campion, D.

AU - Cohen, D.

AU - Dikeos, D.

AU - Duan, J.

AU - Eichhammer, P.

AU - Godard, S.

AU - Hansen, M.

AU - Lerer, F.B.

AU - Liang, K.Y.

AU - Maier, W.

AU - Mallet, J.

AU - Nertney, D. A.

AU - Nestadt, G.

AU - Norton, N.

AU - O'Neill, F.A.

AU - Papadimitriou, G.N.

AU - Ribble, R.

AU - Sanders, A.R.

AU - Silverman, J.M.

AU - Wormley, B.

AU - Arranz, M.J.

AU - Bakker, S.

AU - Bender, S.

AU - Bramon, E.

AU - Collier, D.

AU - Crespo-Facorro, B.

AU - Hall, J.

AU - Iyegbe, C.

AU - Jablensky, A.

AU - Kahn, R.S.

AU - Kalaydjieva, L.

AU - Lawrie, S.M.

AU - Lewis, C.M.

AU - Linszen, D.H.

AU - Mata, I.

AU - McIntosh, A.

AU - Murray, R.M.

AU - Ophoff, R.A.

AU - van Os, J.

AU - Walshe, M.

AU - Weisbrod, M.

AU - Wiersma, D.

AU - Donnely, P.

AU - Barasso, I.

AU - Blackwell, J.M.

AU - Brown, M.A.

AU - Casas, J.P.

AU - Corvin, A.P.

AU - Deloukas, P.

AU - Duncanson, A.

AU - Jankowski, J.

AU - Markus, H.S.

AU - Mathew, C.G.

AU - Palmer, C.N.

AU - Plomin, R.

AU - Rautanen, A.

AU - Sawcer, S.J.

AU - Trembath, R.C.

AU - Viswanathan, A.C.

AU - Wood, N.W.

AU - Spencer, C. C.

AU - Band, G.

AU - Bellenguez, C.

AU - Freeman, C.

AU - Hellenthal, G.

AU - Giannoulatou, E.

AU - Pirinen, M.

AU - Pearson, R.D.

AU - Strange, A.

AU - Su, Z.

AU - Vukcevic, D.

AU - Langford, C.

AU - Hunt, S.E.

AU - Edkins, S.

AU - Gwilliam, R.

AU - Blackburn, H.

AU - Bumpstead, S.

AU - Dronov, S.

AU - Gillman, M.

AU - Gray, E.

AU - Hammond, N.

AU - Jayakumar, A.

AU - McCann, O.T.

AU - Liddle, J.

AU - Potter, S.C.

AU - Ravindrarajah, R.

AU - Ricketts, M.

AU - Tashakkori-Ghanbaria, A.

AU - Waller, M.J.

AU - Weston, P.

AU - Widaa, S.

AU - Whittaker, P.

AU - Barrroso, I.

AU - McCarthy, M.I.

AU - Spencer, C.C.

AU - Stefansson, K.

AU - Scolnick, E.

AU - Purcell, S.

AU - McCarroll, S.A.

AU - Sklar, P.

AU - Hultman, C. M.

AU - Sullivan, P.F.

N1 - Multicenter Genetic Studies of Schizophrenia Consortium;Psychosis Endophenotypes International Consort; Wellcome Trust Case Control Consortium 2

PY - 2013

Y1 - 2013

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. © 2013 Nature America, Inc. All rights reserved.

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. © 2013 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.2742

DO - 10.1038/ng.2742

M3 - Article

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

Abstract

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