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Genome-wide association study identifies five new schizophrenia loci

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Overview

authors

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

publication date

  • October 2011

journal

  • Nature Genetics  Journal

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 × 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 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

subject areas

  • Alleles
  • Bipolar Disorder
  • Case-Control Studies
  • European Continental Ancestry Group
  • Female
  • Gene Dosage
  • Gene Expression Regulation
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome, Human
  • Genome-Wide Association Study
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • MicroRNAs
  • Mutation
  • Polymorphism, Single Nucleotide
  • Schizophrenia
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Identity

PubMed Central ID

  • PMC3303194

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.940

PubMed ID

  • 21926974
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Additional Document Info

start page

  • 969

end page

  • 76

volume

  • 43

issue

  • 10

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