Genome-wide association study identifies five new schizophrenia loci.
|Title||Genome-wide association study identifies five new schizophrenia loci.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Ripke, S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA, Lin D-Y, Duan J, Ophoff RA, Andreassen OA et al.|
|Corporate Authors||Schizophrenia Psychiatric Genome-Wide Association Study(GWAS) Consortium|
|Date Published||2011 Oct|
|Keywords||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|
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)).
|Alternate Journal||Nat. Genet.|