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

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1354 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 languageEnglish
Pages (from-to)969-976
Number of pages8
JournalNature Genetics
Volume43
Issue number10
Early online date18 Sep 2011
DOIs
Publication statusPublished - Oct 2011

ASJC Scopus subject areas

  • Genetics

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