Genome-wide Association Study Identifies Five New Schizophrenia Loci

Nat Genet. 2011 Sep 18;43(10):969-76. doi: 10.1038/ng.940.

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)).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / genetics
  • MicroRNAs / metabolism
  • Mutation
  • Polymorphism, Single Nucleotide*
  • Schizophrenia / genetics*

Substances

  • MicroRNAs

Grant support