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Genome-wide association study identifies five new schizophrenia loci

Journal Article


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). �� 2011 Nature America, Inc. All rights reserved.

Publication Date


  • 2011

Citation


  • Ripke, S., Sanders, A. R., Kendler, K. S., Levinson, D. F., Sklar, P., Holmans, P. A., . . . Krasucki, R. (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43(10), 969-978. doi:10.1038/ng.940

Scopus Eid


  • 2-s2.0-80053384370

Web Of Science Accession Number


Start Page


  • 969

End Page


  • 978

Volume


  • 43

Issue


  • 10

Place Of Publication


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). �� 2011 Nature America, Inc. All rights reserved.

Publication Date


  • 2011

Citation


  • Ripke, S., Sanders, A. R., Kendler, K. S., Levinson, D. F., Sklar, P., Holmans, P. A., . . . Krasucki, R. (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43(10), 969-978. doi:10.1038/ng.940

Scopus Eid


  • 2-s2.0-80053384370

Web Of Science Accession Number


Start Page


  • 969

End Page


  • 978

Volume


  • 43

Issue


  • 10

Place Of Publication