Genome-wide association study identifies five new schizophrenia loci Public Deposited

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Creator
  • Lin, Danyu
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
  • The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium
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).
Date of publication
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Identifier
  • doi:10.1038/ng.940
  • 2-s2.0-80053384370
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Nature Genetics
Journal volume
  • 43
Journal issue
  • 10
Page start
  • 969
Page end
  • 978
Language
  • English
Version
  • Postprint
ISSN
  • 1061-4036
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