Genome-wide association study identifies five new schizophrenia loci

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., St. Clair, D., 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., Jönsson, E. G., Bitter, I., Pietiläinen, 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., Børglum, 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, M., Glenthøj, 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., Jürgens, G., Kahn, R. S., 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., Lönnqvist, 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., Nöthen, M. M., O'Dushlaine, C. T., Olincy, A., Olsen, L., O'Neill, F. A., Ørntoft, 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., Réthelyi, J. M., Ribble, R., Rietschel, M., Riley, B. P., Ruggeri, M., Schall, U., Schulze, T. G., Schwab, S. G., Scott, R. J., Shi, J., Sigurdsson, E., Silverman, J. M., Spencer, C. C. A., Stefansson, K., Strange, A., Strengman, E., Stroup, T. S., Suvisaari, J., Terenius, L., 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. (2011) Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43(10), pp. 969-976.

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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).

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ID Code: 89358
Item Type: Journal Article
Refereed: Yes
Keywords: microRNA, article, bipolar disorder, European American, female, gene locus, gene replication, genetic association, genetic identification, genetic transcription, genetic variability, genome analysis, human, intron, major clinical study, male, priority journal, schizophrenia, Alleles, Case-Control Studies, European Continental Ancestry Group, Gene Dosage, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Haplotypes, Humans, Linkage Disequilibrium, Logistic Models, MicroRNAs, Mutation, Polymorphism, Single Nucleotide
DOI: 10.1038/ng.940
ISSN: 1061-4036
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 Nature America, Inc.
Deposited On: 21 Oct 2015 02:22
Last Modified: 26 Feb 2016 04:11

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