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Genome-wide association study identifies five new schizophrenia loci

Ripke, Stephan and Sanders, Alan R and Kendler, Kenneth S and Levinson, Douglas F and Sklar, Pamela and Holmans, Peter A and Lin, Dan-Yu and Duan, Jubao and Ophoff, Roel A and Andreassen, Ole A and Scolnick, Edward and Cichon, Sven and St Clair, David and Corvin, Aiden and Gurling, Hugh and Werge, Thomas and Rujescu, Dan and Blackwood, Douglas H R and Pato, Carlos N and Malhotra, Anil K and Purcell, Shaun and Dudbridge, Frank and Neale, Benjamin M and Rossin, Lizzy and Visscher, Peter M and Posthuma, Danielle and Ruderfer, Douglas M and Fanous, Ayman and Stefansson, Hreinn and Steinberg, Stacy and Mowry, Bryan J and Golimbet, Vera and De Hert, Marc and Jönsson, Erik G and Bitter, István and Pietiläinen, Olli P H and Collier, David A and Tosato, Sarah and Agartz, Ingrid and Albus, Margot and Alexander, Madeline and Amdur, Richard L and Amin, Farooq and Bass, Nicholas and Bergen, Sarah E and Black, Donald W and Børglum, Anders D and Brown, Matthew A and Bruggeman, Richard and Pickard, Ben, The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43 (10). pp. 969-976.

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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)).