Genome-wide association study identifies five new schizophrenia loci

S. Ripke; P. Sklar; L. Rossin; D.M. Ruderfer; S.E. Bergen; M.J. Daly; A.R. Sanders; J. Duan; P.V. Gejman; K.S. Kendler; B.S. Maher; R. Ribble; B.P. Riley; B. Wormley; A. Fanous; D.F. Levinson; M. Alexander; J.M. Silverman; P.A. Holmans; N. Craddock; S. Dwyer; L. Georgieva; M. Hamshere; G.K. Kirov; V. Moskvina; I. Nikolov; N. Norton; M.J. Owen; H.J. Williams; N.M. Williams; S. Zammit; M.C. O'Donovan; D.-Y. Lin; R.A. Ophoff; E. Strengman; R.M. Cantor; N.B. Freimer; O.A. Andreassen; I. Agartz; S. Djurovic; M. Mattingsdal; I. Melle; E. Scolnick; S. Purcell; B.M. Neale; S. Cichon; M. Mattheisen; M.M. Nöthen; D. St. Clair; A. Corvin; P. Cormican; G. Donohoe; M. Gill; E. Kenny; D.W. Morris; C.T. O'Dushlaine; E.M. Quinn; H. Gurling; N. Bass; K. Choudhury; S. Datta; R. Krasucki; J. Lawrence; A. McQuillin; J. Pimm; V. Puri; T. Werge; L. Duong; T. Hansen; A. Ingason; K.D. Jakobsen; L. Olsen; H.B. Rasmussen; J.H. Thygesen; D. Rujescu; M. Friedl; I. Giegling; A.M. Hartmann; H. Konnerth; B. Konte; D.H.R. Blackwood; A.W. MacLean; P. Malloy; K.A. McGhee; A. McIntosh; C.N. Pato; M.T. Pato; A.K. Malhotra; T. Lencz; F. Dudbridge; P.M. Visscher; D. Posthuma; R.L. Amdur; H. Stefansson; S. Steinberg; K. Stefansson; B.J. Mowry; J.J. McGrath; D.A. Nertney; V. Golimbet; M. De Hert; R. Van Winkel; E.G. Jönsson; L. Terenius; I. Bitter; J.M. Réthelyi; O.P.H. Pietiläinen; L. Peltonen; D.A. Collier; S. Tosato; M. Ruggeri; M. Albus; F. Amin; D.W. Black; A.D. Børglum; D. Demontis; O. Mors; M.A. Brown; P.A. Danoy; R. Bruggeman; D. Wiersma; N.G. Buccola; W.F. Byerley; W. Cahn; R.S. Kahn; V.J. Carr; S.V. Catts; C.R. Cloninger; L. De Haan; D.H. Linszen; D. Dikeos; G. Papadimitriou; P. Donnelly; C.C.A. Spencer; A. Strange; A. Fink-Jensen; R. Freedman; A. Olincy; B. Glenthøj; S. Godard; M. Hansen; F.A. Henskens; D.M. Hougaard; C.M. Hultman; P. Lichtenstein; P.F. Sullivan; A.V. Jablensky; M. Jay; C. Laurent; G. Jürgens; M.C. Keller; G. Kenis; Y. Kim; L. Krabbendam; I. Myin-Germeys; J. Van Os; V.K. Lasseter; G. Nestadt; A.E. Pulver; F.B. Lerer; K.-Y. Liang; J.A. Lieberman; T.S. Stroup; J. Lönnqvist; J. Suvisaari; C.M. Loughland; W. Maier; M. Rietschel; J. Mallet; D.E. McLean; P.T. Michie; U. Schall; V. Milanova; P.B. Mortensen; P. Muglia; J. Nielsen; M. Nordentoft; F.A. O'Neill; T.F. Ørntoft; C. Pantelis; H. Petursson; E. Sigurdsson; B. Pickard; D. Quested; T.G. Schulze; S.G. Schwab; D.B. Wildenauer; R.J. Scott; J. Shi; S. Thirumalai; S. Timm; D. Toncheva; E. Van Den Oord; J. Veldink; D. Walsh; A.G. Wang

doi:10.1038/ng.940

Genome-wide association study identifies five new schizophrenia loci

S. Ripke, P. Sklar, L. Rossin, D.M. Ruderfer, S.E. Bergen, M.J. Daly, A.R. Sanders, J. Duan, P.V. Gejman, K.S. Kendler, B.S. Maher, R. Ribble, B.P. Riley, B. Wormley, A. Fanous, D.F. Levinson, M. Alexander, J.M. Silverman, P.A. Holmans, N. CraddockS. Dwyer, L. Georgieva, M. Hamshere, G.K. Kirov, V. Moskvina, I. Nikolov, N. Norton, M.J. Owen, H.J. Williams, N.M. Williams, S. Zammit, M.C. O'Donovan, D.-Y. Lin, R.A. Ophoff, E. Strengman, R.M. Cantor, N.B. Freimer, O.A. Andreassen, I. Agartz, S. Djurovic, M. Mattingsdal, I. Melle, E. Scolnick, S. Purcell, B.M. Neale, S. Cichon, M. Mattheisen, M.M. Nöthen, D. St. Clair, A. Corvin, P. Cormican, G. Donohoe, M. Gill, E. Kenny, D.W. Morris, C.T. O'Dushlaine, E.M. Quinn, H. Gurling, N. Bass, K. Choudhury, S. Datta, R. Krasucki, J. Lawrence, A. McQuillin, J. Pimm, V. Puri, T. Werge, L. Duong, T. Hansen, A. Ingason, K.D. Jakobsen, L. Olsen, H.B. Rasmussen, J.H. Thygesen, D. Rujescu, M. Friedl, I. Giegling, A.M. Hartmann, H. Konnerth, B. Konte, D.H.R. Blackwood, A.W. MacLean, P. Malloy, K.A. McGhee, A. McIntosh, C.N. Pato, M.T. Pato, A.K. Malhotra, T. Lencz, F. Dudbridge, P.M. Visscher, D. Posthuma, R.L. Amdur, H. Stefansson, S. Steinberg, K. Stefansson, B.J. Mowry, J.J. McGrath, D.A. Nertney, V. Golimbet, M. De Hert, R. Van Winkel, E.G. Jönsson, L. Terenius, I. Bitter, J.M. Réthelyi, O.P.H. Pietiläinen, L. Peltonen, D.A. Collier, S. Tosato, M. Ruggeri, M. Albus, F. Amin, D.W. Black, A.D. Børglum, D. Demontis, O. Mors, M.A. Brown, P.A. Danoy, R. Bruggeman, D. Wiersma, N.G. Buccola, W.F. Byerley, W. Cahn, R.S. Kahn, V.J. Carr, S.V. Catts, C.R. Cloninger, L. De Haan, D.H. Linszen, D. Dikeos, G. Papadimitriou, P. Donnelly, C.C.A. Spencer, A. Strange, A. Fink-Jensen, R. Freedman, A. Olincy, B. Glenthøj, S. Godard, M. Hansen, F.A. Henskens, D.M. Hougaard, C.M. Hultman, P. Lichtenstein, P.F. Sullivan, A.V. Jablensky, M. Jay, C. Laurent, G. Jürgens, M.C. Keller, G. Kenis, Y. Kim, L. Krabbendam, I. Myin-Germeys, J. Van Os, V.K. Lasseter, G. Nestadt, A.E. Pulver, F.B. Lerer, K.-Y. Liang, J.A. Lieberman, T.S. Stroup, J. Lönnqvist, J. Suvisaari, C.M. Loughland, W. Maier, M. Rietschel, J. Mallet, D.E. McLean, P.T. Michie, U. Schall, V. Milanova, P.B. Mortensen, P. Muglia, J. Nielsen, M. Nordentoft, F.A. O'Neill, T.F. Ørntoft, C. Pantelis, H. Petursson, E. Sigurdsson, B. Pickard, D. Quested, T.G. Schulze, S.G. Schwab, D.B. Wildenauer, R.J. Scott, J. Shi, S. Thirumalai, S. Timm, D. Toncheva, E. Van Den Oord, J. Veldink, D. Walsh, A.G. Wang

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

1612 Citations (Scopus)

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 language	English
Pages (from-to)	969-976
Number of pages	8
Journal	Nature Genetics
Volume	43
Issue number	10
Early online date	18 Sept 2011
DOIs	https://doi.org/10.1038/ng.940
Publication status	Published - Oct 2011

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.940

Cite this

Ripke, S., Sklar, P., Rossin, L., Ruderfer, D. M., Bergen, S. E., Daly, M. J., Sanders, A. R., Duan, J., Gejman, P. V., Kendler, K. S., Maher, B. S., Ribble, R., Riley, B. P., Wormley, B., Fanous, A., Levinson, D. F., Alexander, M., Silverman, J. M., Holmans, P. A., ... Wang, A. G. (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43(10), 969-976. https://doi.org/10.1038/ng.940

@article{eb2866c5f2be41a2939ac34d799ad1db,

title = "Genome-wide association study identifies five new schizophrenia loci",

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)).",

author = "S. Ripke and P. Sklar and L. Rossin and D.M. Ruderfer and S.E. Bergen and M.J. Daly and A.R. Sanders and J. Duan and P.V. Gejman and K.S. Kendler and B.S. Maher and R. Ribble and B.P. Riley and B. Wormley and A. Fanous and D.F. Levinson and M. Alexander and J.M. Silverman and P.A. Holmans and N. Craddock and S. Dwyer and L. Georgieva and M. Hamshere and G.K. Kirov and V. Moskvina and I. Nikolov and N. Norton and M.J. Owen and H.J. Williams and N.M. Williams and S. Zammit and M.C. O'Donovan and D.-Y. Lin and R.A. Ophoff and E. Strengman and R.M. Cantor and N.B. Freimer and O.A. Andreassen and I. Agartz and S. Djurovic and M. Mattingsdal and I. Melle and E. Scolnick and S. Purcell and B.M. Neale and S. Cichon and M. Mattheisen and M.M. N{\"o}then and {St. Clair}, D. and A. Corvin and P. Cormican and G. Donohoe and M. Gill and E. Kenny and D.W. Morris and C.T. O'Dushlaine and E.M. Quinn and H. Gurling and N. Bass and K. Choudhury and S. Datta and R. Krasucki and J. Lawrence and A. McQuillin and J. Pimm and V. Puri and T. Werge and L. Duong and T. Hansen and A. Ingason and K.D. Jakobsen and L. Olsen and H.B. Rasmussen and J.H. Thygesen and D. Rujescu and M. Friedl and I. Giegling and A.M. Hartmann and H. Konnerth and B. Konte and D.H.R. Blackwood and A.W. MacLean and P. Malloy and K.A. McGhee and A. McIntosh and C.N. Pato and M.T. Pato and A.K. Malhotra and T. Lencz and F. Dudbridge and P.M. Visscher and D. Posthuma and R.L. Amdur and H. Stefansson and S. Steinberg and K. Stefansson and B.J. Mowry and J.J. McGrath and D.A. Nertney and V. Golimbet and {De Hert}, M. and {Van Winkel}, R. and E.G. J{\"o}nsson and L. Terenius and I. Bitter and J.M. R{\'e}thelyi and O.P.H. Pietil{\"a}inen and L. Peltonen and D.A. Collier and S. Tosato and M. Ruggeri and M. Albus and F. Amin and D.W. Black and A.D. B{\o}rglum and D. Demontis and O. Mors and M.A. Brown and P.A. Danoy and R. Bruggeman and D. Wiersma and N.G. Buccola and W.F. Byerley and W. Cahn and R.S. Kahn and V.J. Carr and S.V. Catts and C.R. Cloninger and {De Haan}, L. and D.H. Linszen and D. Dikeos and G. Papadimitriou and P. Donnelly and C.C.A. Spencer and A. Strange and A. Fink-Jensen and R. Freedman and A. Olincy and B. Glenth{\o}j and S. Godard and M. Hansen and F.A. Henskens and D.M. Hougaard and C.M. Hultman and P. Lichtenstein and P.F. Sullivan and A.V. Jablensky and M. Jay and C. Laurent and G. J{\"u}rgens and M.C. Keller and G. Kenis and Y. Kim and L. Krabbendam and I. Myin-Germeys and {Van Os}, J. and V.K. Lasseter and G. Nestadt and A.E. Pulver and F.B. Lerer and K.-Y. Liang and J.A. Lieberman and T.S. Stroup and J. L{\"o}nnqvist and J. Suvisaari and C.M. Loughland and W. Maier and M. Rietschel and J. Mallet and D.E. McLean and P.T. Michie and U. Schall and V. Milanova and P.B. Mortensen and P. Muglia and J. Nielsen and M. Nordentoft and F.A. O'Neill and T.F. {\O}rntoft and C. Pantelis and H. Petursson and E. Sigurdsson and B. Pickard and D. Quested and T.G. Schulze and S.G. Schwab and D.B. Wildenauer and R.J. Scott and J. Shi and S. Thirumalai and S. Timm and D. Toncheva and {Van Den Oord}, E. and J. Veldink and D. Walsh and A.G. Wang",

year = "2011",

month = oct,

doi = "10.1038/ng.940",

language = "English",

volume = "43",

pages = "969--976",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "10",

}

Ripke, S, Sklar, P, Rossin, L, Ruderfer, DM, Bergen, SE, Daly, MJ, Sanders, AR, Duan, J, Gejman, PV, Kendler, KS, Maher, BS, Ribble, R, Riley, BP, Wormley, B, Fanous, A, Levinson, DF, Alexander, M, Silverman, JM, Holmans, PA, Craddock, N, Dwyer, S, Georgieva, L, Hamshere, M, Kirov, GK, Moskvina, V, Nikolov, I, Norton, N, Owen, MJ, Williams, HJ, Williams, NM, Zammit, S, O'Donovan, MC, Lin, D-Y, Ophoff, RA, Strengman, E, Cantor, RM, Freimer, NB, Andreassen, OA, Agartz, I, Djurovic, S, Mattingsdal, M, Melle, I, Scolnick, E, Purcell, S, Neale, BM, Cichon, S, Mattheisen, M, Nöthen, MM, St. Clair, D, Corvin, A, Cormican, P, Donohoe, G, Gill, M, Kenny, E, Morris, DW, O'Dushlaine, CT, Quinn, EM, Gurling, H, Bass, N, Choudhury, K, Datta, S, Krasucki, R, Lawrence, J, McQuillin, A, Pimm, J, Puri, V, Werge, T, Duong, L, Hansen, T, Ingason, A, Jakobsen, KD, Olsen, L, Rasmussen, HB, Thygesen, JH, Rujescu, D, Friedl, M, Giegling, I, Hartmann, AM, Konnerth, H, Konte, B, Blackwood, DHR, MacLean, AW, Malloy, P, McGhee, KA, McIntosh, A, Pato, CN, Pato, MT, Malhotra, AK, Lencz, T, Dudbridge, F, Visscher, PM, Posthuma, D, Amdur, RL, Stefansson, H, Steinberg, S, Stefansson, K, Mowry, BJ, McGrath, JJ, Nertney, DA, Golimbet, V, De Hert, M, Van Winkel, R, Jönsson, EG, Terenius, L, Bitter, I, Réthelyi, JM, Pietiläinen, OPH, Peltonen, L, Collier, DA, Tosato, S, Ruggeri, M, Albus, M, Amin, F, Black, DW, Børglum, AD, Demontis, D, Mors, O, Brown, MA, Danoy, PA, Bruggeman, R, Wiersma, D, Buccola, NG, Byerley, WF, Cahn, W, Kahn, RS, Carr, VJ, Catts, SV, Cloninger, CR, De Haan, L, Linszen, DH, Dikeos, D, Papadimitriou, G, Donnelly, P, Spencer, CCA, Strange, A, Fink-Jensen, A, Freedman, R, Olincy, A, Glenthøj, B, Godard, S, Hansen, M, Henskens, FA, Hougaard, DM, Hultman, CM, Lichtenstein, P, Sullivan, PF, Jablensky, AV, Jay, M, Laurent, C, Jürgens, G, Keller, MC, Kenis, G, Kim, Y, Krabbendam, L, Myin-Germeys, I, Van Os, J, Lasseter, VK, Nestadt, G, Pulver, AE, Lerer, FB, Liang, K-Y, Lieberman, JA, Stroup, TS, Lönnqvist, J, Suvisaari, J, Loughland, CM, Maier, W, Rietschel, M, Mallet, J, McLean, DE, Michie, PT, Schall, U, Milanova, V, Mortensen, PB, Muglia, P, Nielsen, J, Nordentoft, M, O'Neill, FA, Ørntoft, TF, Pantelis, C, Petursson, H, Sigurdsson, E, Pickard, B, Quested, D, Schulze, TG, Schwab, SG, Wildenauer, DB, Scott, RJ, Shi, J, Thirumalai, S, Timm, S, Toncheva, D, Van Den Oord, E, Veldink, J, Walsh, D & Wang, AG 2011, 'Genome-wide association study identifies five new schizophrenia loci', Nature Genetics, vol. 43, no. 10, pp. 969-976. https://doi.org/10.1038/ng.940

TY - JOUR

T1 - Genome-wide association study identifies five new schizophrenia loci

AU - Ripke, S.

AU - Sklar, P.

AU - Rossin, L.

AU - Ruderfer, D.M.

AU - Bergen, S.E.

AU - Daly, M.J.

AU - Sanders, A.R.

AU - Duan, J.

AU - Gejman, P.V.

AU - Kendler, K.S.

AU - Maher, B.S.

AU - Ribble, R.

AU - Riley, B.P.

AU - Wormley, B.

AU - Fanous, A.

AU - Levinson, D.F.

AU - Alexander, M.

AU - Silverman, J.M.

AU - Holmans, P.A.

AU - Craddock, N.

AU - Dwyer, S.

AU - Georgieva, L.

AU - Hamshere, M.

AU - Kirov, G.K.

AU - Moskvina, V.

AU - Nikolov, I.

AU - Norton, N.

AU - Owen, M.J.

AU - Williams, H.J.

AU - Williams, N.M.

AU - Zammit, S.

AU - O'Donovan, M.C.

AU - Lin, D.-Y.

AU - Ophoff, R.A.

AU - Strengman, E.

AU - Cantor, R.M.

AU - Freimer, N.B.

AU - Andreassen, O.A.

AU - Agartz, I.

AU - Djurovic, S.

AU - Mattingsdal, M.

AU - Melle, I.

AU - Scolnick, E.

AU - Purcell, S.

AU - Neale, B.M.

AU - Cichon, S.

AU - Mattheisen, M.

AU - Nöthen, M.M.

AU - St. Clair, D.

AU - Corvin, A.

AU - Cormican, P.

AU - Donohoe, G.

AU - Gill, M.

AU - Kenny, E.

AU - Morris, D.W.

AU - O'Dushlaine, C.T.

AU - Quinn, E.M.

AU - Gurling, H.

AU - Bass, N.

AU - Choudhury, K.

AU - Datta, S.

AU - Krasucki, R.

AU - Lawrence, J.

AU - McQuillin, A.

AU - Pimm, J.

AU - Puri, V.

AU - Werge, T.

AU - Duong, L.

AU - Hansen, T.

AU - Ingason, A.

AU - Jakobsen, K.D.

AU - Olsen, L.

AU - Rasmussen, H.B.

AU - Thygesen, J.H.

AU - Rujescu, D.

AU - Friedl, M.

AU - Giegling, I.

AU - Hartmann, A.M.

AU - Konnerth, H.

AU - Konte, B.

AU - Blackwood, D.H.R.

AU - MacLean, A.W.

AU - Malloy, P.

AU - McGhee, K.A.

AU - McIntosh, A.

AU - Pato, C.N.

AU - Pato, M.T.

AU - Malhotra, A.K.

AU - Lencz, T.

AU - Dudbridge, F.

AU - Visscher, P.M.

AU - Posthuma, D.

AU - Amdur, R.L.

AU - Stefansson, H.

AU - Steinberg, S.

AU - Stefansson, K.

AU - Mowry, B.J.

AU - McGrath, J.J.

AU - Nertney, D.A.

AU - Golimbet, V.

AU - De Hert, M.

AU - Van Winkel, R.

AU - Jönsson, E.G.

AU - Terenius, L.

AU - Bitter, I.

AU - Réthelyi, J.M.

AU - Pietiläinen, O.P.H.

AU - Peltonen, L.

AU - Collier, D.A.

AU - Tosato, S.

AU - Ruggeri, M.

AU - Albus, M.

AU - Amin, F.

AU - Black, D.W.

AU - Børglum, A.D.

AU - Demontis, D.

AU - Mors, O.

AU - Brown, M.A.

AU - Danoy, P.A.

AU - Bruggeman, R.

AU - Wiersma, D.

AU - Buccola, N.G.

AU - Byerley, W.F.

AU - Cahn, W.

AU - Kahn, R.S.

AU - Carr, V.J.

AU - Catts, S.V.

AU - Cloninger, C.R.

AU - De Haan, L.

AU - Linszen, D.H.

AU - Dikeos, D.

AU - Papadimitriou, G.

AU - Donnelly, P.

AU - Spencer, C.C.A.

AU - Strange, A.

AU - Fink-Jensen, A.

AU - Freedman, R.

AU - Olincy, A.

AU - Glenthøj, B.

AU - Godard, S.

AU - Hansen, M.

AU - Henskens, F.A.

AU - Hougaard, D.M.

AU - Hultman, C.M.

AU - Lichtenstein, P.

AU - Sullivan, P.F.

AU - Jablensky, A.V.

AU - Jay, M.

AU - Laurent, C.

AU - Jürgens, G.

AU - Keller, M.C.

AU - Kenis, G.

AU - Kim, Y.

AU - Krabbendam, L.

AU - Myin-Germeys, I.

AU - Van Os, J.

AU - Lasseter, V.K.

AU - Nestadt, G.

AU - Pulver, A.E.

AU - Lerer, F.B.

AU - Liang, K.-Y.

AU - Lieberman, J.A.

AU - Stroup, T.S.

AU - Lönnqvist, J.

AU - Suvisaari, J.

AU - Loughland, C.M.

AU - Maier, W.

AU - Rietschel, M.

AU - Mallet, J.

AU - McLean, D.E.

AU - Michie, P.T.

AU - Schall, U.

AU - Milanova, V.

AU - Mortensen, P.B.

AU - Muglia, P.

AU - Nielsen, J.

AU - Nordentoft, M.

AU - O'Neill, F.A.

AU - Ørntoft, T.F.

AU - Pantelis, C.

AU - Petursson, H.

AU - Sigurdsson, E.

AU - Pickard, B.

AU - Quested, D.

AU - Schulze, T.G.

AU - Schwab, S.G.

AU - Wildenauer, D.B.

AU - Scott, R.J.

AU - Shi, J.

AU - Thirumalai, S.

AU - Timm, S.

AU - Toncheva, D.

AU - Van Den Oord, E.

AU - Veldink, J.

AU - Walsh, D.

AU - Wang, A.G.

PY - 2011/10

Y1 - 2011/10

N2 - 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)).

AB - 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)).

UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-80053384370&md5=6fb1cad1cc387567b068202263888e27

U2 - 10.1038/ng.940

DO - 10.1038/ng.940

M3 - Article

C2 - 21926974

SN - 1061-4036

VL - 43

SP - 969

EP - 976

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

Genome-wide association study identifies five new schizophrenia loci

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