Genome-wide association analysis identifies 13 new risk loci for schizophrenia

S Ripke, C O'Dushlaine, K Chambert, JL Moran, AK Kahler, S Akterin, SE Bergen, AL Collins, JJ Crowley, M Fromer, Y. Kim, SH Lee, PKE Magnusson, N Sanchez, EA Stahl, S Williams, NR Wray, K Xia, F Bettella, AD BorglumBK Bulik-Sullivan, P Cormican, N Craddock, C de Leeuw, N Durmishi, M Gill, V Golimbet, ML Hamshere, P Holmans, DM Hougaard, KS Kendler, K Lin, DW Morris, O Mors, PB Mortensen, BM Neale, FA O'Neill, MJ Owen, MP Milovancevic, Daniëlle Posthuma, J Powell, AL Richards, BP Riley, D Ruderfer, D Rujescu, E Sigurdsson, T Silagadze, AB Smit, H Stefansson, S Steinberg, J Suvisaari, S Tosato, M Verhage, JT Walters, E Bramon, AP Corvin, MC O'Donovan, K Stefansson, E Scolnick, S Purcell, SA McCarroll, P Sklar, CM Hultman, PF Sullivan

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Abstract

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.
Original languageUndefined/Unknown
Pages (from-to)1150-U282
JournalNature Genetics
Volume45
Issue number10
DOIs
Publication statusPublished - 2013

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  • EMC NIHES-04-55-01

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