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

Genome-wide association study identifies five new schizophrenia loci

Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium  1
Collaborators, Affiliations

Genome-wide association study identifies five new schizophrenia loci

Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium. Nat Genet. .

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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Conflict of interest statement

COMPETING FINANCIAL INTERESTS

The authors declare competing financial interests: details accompany the full-text HTML version of the paper at http://www.nature.com/naturegenetics/.

Figures

Figure 1
Figure 1
Manhattan plot for stages 1 and 2. Standard −log10 P plot of the study results. For the stage 1 results, 16 regions with one or more SNP achieving P < 10−6 are highlighted in color and labeled with the name of the nearest gene. SNPs selected for stage 2 replication are highlighted, with the resulting combined P value after replication (that is, after incorporation of stage 2 results) indicated by the large diamonds. Blue highlighting indicates SNPs that were less significantly associated after replication, and pink highlighting indicates SNPs that were more significantly associated after replication.
Figure 2
Figure 2
Regional association plots for five new schizophrenia loci. Regional P value plots for each of the five new schizophrenia loci: 1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33. Each plot shows the most associated SNP (key SNP) and its genomic region from the first column of Table 2: stage 1 scan results for each SNP ± 200 kb to the key SNP are shown. On the x axis is the genomic position, and on the y axis is −log10 P. Larger SNP symbols indicate higher LD (based on HapMap 3 data) to the key SNP than smaller SNP symbols. Color coding (from red to blue) denotes LD information; see also the legend within the plot.
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