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Genome-wide association study identifies five new schizophrenia loci.

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)).

Pubmed ID: 21926974

Authors

  • Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium

Journal

Nature genetics

Publication Data

October 29, 2011

Associated Grants

  • Agency: Wellcome Trust, Id: 090532
  • Agency: Medical Research Council, Id: G0800509
  • Agency: Medical Research Council, Id: G0801418B
  • Agency: Medical Research Council, Id: G1000708
  • Agency: Medical Research Council, Id: G1000718
  • Agency: Medical Research Council, Id: G9817803B
  • Agency: NIMH NIH HHS, Id: K01 MH085812
  • Agency: NIMH NIH HHS, Id: K23 MH001760
  • Agency: NCI NIH HHS, Id: P01 CA142538
  • Agency: NIMH NIH HHS, Id: P30 MH074543
  • Agency: NIMH NIH HHS, Id: P50 MH066392
  • Agency: NCI NIH HHS, Id: R01 CA082659
  • Agency: NCI NIH HHS, Id: R01 CA082659-12
  • Agency: NIMH NIH HHS, Id: R01 MH052618
  • Agency: NIMH NIH HHS, Id: R01 MH058693
  • Agency: NIMH NIH HHS, Id: R01 MH059565
  • Agency: NIMH NIH HHS, Id: R01 MH059566
  • Agency: NIMH NIH HHS, Id: R01 MH059571
  • Agency: NIMH NIH HHS, Id: R01 MH059586
  • Agency: NIMH NIH HHS, Id: R01 MH059587
  • Agency: NIMH NIH HHS, Id: R01 MH059588
  • Agency: NIMH NIH HHS, Id: R01 MH060870
  • Agency: NIMH NIH HHS, Id: R01 MH060879
  • Agency: NIMH NIH HHS, Id: R01 MH061675
  • Agency: NIMH NIH HHS, Id: R01 MH061884
  • Agency: NIMH NIH HHS, Id: R01 MH062276
  • Agency: NIMH NIH HHS, Id: R01 MH067257
  • Agency: NIMH NIH HHS, Id: R01 MH068881
  • Agency: NIMH NIH HHS, Id: R01 MH068921
  • Agency: NIMH NIH HHS, Id: R01 MH068922
  • Agency: NIMH NIH HHS, Id: R01 MH071681
  • Agency: NIMH NIH HHS, Id: R01 MH074027
  • Agency: NIMH NIH HHS, Id: R01 MH077139
  • Agency: NIMH NIH HHS, Id: R01 MH078075
  • Agency: NIMH NIH HHS, Id: R01 MH079800
  • Agency: NIMH NIH HHS, Id: R01 MH080403
  • Agency: NIMH NIH HHS, Id: R01 MH081800
  • Agency: NIMH NIH HHS, Id: R01 MH083094
  • Agency: NIMH NIH HHS, Id: R01 MH084098
  • Agency: NIMH NIH HHS, Id: R01 MH085548
  • Agency: NIGMS NIH HHS, Id: R37 GM047845
  • Agency: NIGMS NIH HHS, Id: R37 GM047845-21
  • Agency: NIGMS NIH HHS, Id: T32 GM007753
  • Agency: NIMH NIH HHS, Id: U01 MH046276
  • Agency: NIMH NIH HHS, Id: U01 MH046289
  • Agency: NIMH NIH HHS, Id: U01 MH046318
  • Agency: NIMH NIH HHS, Id: U01 MH079469
  • Agency: NIMH NIH HHS, Id: U01 MH079470
  • Agency: NIMH NIH HHS, Id: U01 MH085508
  • Agency: NIMH NIH HHS, Id: U01 MH085513
  • Agency: NIMH NIH HHS, Id: U01 MH085515
  • Agency: NIMH NIH HHS, Id: U01 MH085518
  • Agency: NIMH NIH HHS, Id: U01 MH085520
  • Agency: NIMH NIH HHS, Id: U01 MH094421
  • Agency: NCRR NIH HHS, Id: U54 RR020278

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
  • Mutation
  • Polymorphism, Single Nucleotide
  • Schizophrenia