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

• Published in: Nature genetics Vol. 45; no. 10; pp. 1150 - 1159
• Main Authors: Ripke, Stephan, O'Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L, Kähler, Anna K, Akterin, Susanne, Bergen, Sarah E, Collins, Ann L, Crowley, James J, Fromer, Menachem, Kim, Yunjung, Lee, Sang Hong, Magnusson, Patrik K E, Sanchez, Nick, Stahl, Eli A, Williams, Stephanie, Wray, Naomi R, Xia, Kai, Bettella, Francesco, Borglum, Anders D, Bulik-Sullivan, Brendan K, Cormican, Paul, Craddock, Nick, de Leeuw, Christiaan, Durmishi, Naser, Gill, Michael, Golimbet, Vera, Hamshere, Marian L, Holmans, Peter, Hougaard, David M, Kendler, Kenneth S, Lin, Kuang, Morris, Derek W, Mors, Ole, Mortensen, Preben B, Neale, Benjamin M, O'Neill, Francis A, Owen, Michael J, Milovancevic, Milica Pejovic, Posthuma, Danielle, Powell, John, Richards, Alexander L, Riley, Brien P, Ruderfer, Douglas, Rujescu, Dan, Sigurdsson, Engilbert, Silagadze, Teimuraz, Smit, August B, Stefansson, Hreinn, Steinberg, Stacy, Suvisaari, Jaana, Tosato, Sarah, Verhage, Matthijs, Walters, James T, Bramon, Elvira, Corvin, Aiden P, O'Donovan, Michael C, Stefansson, Kari, Scolnick, Edward, Purcell, Shaun, McCarroll, Steven A, Sklar, Pamela, Hultman, Christina M, Sullivan, Patrick F
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2013; Nature Publishing Group
• Subjects: 692/699/476/1799; Agriculture; Animal Genetics and Genomics; Biomedicine; Cancer Research; Case-Control Studies; Chromosomes; Councils; Female; Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi; Gene Function; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Genomics; Human Genetics; Humans; Hälsovetenskap; Klinisk medicin; Male; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Mental disorders; Offspring; Polymorphism, Single Nucleotide; Psykiatri; Public health; Risk factors; Sample size; Schizophrenia; Schizophrenia - genetics; Single nucleotide polymorphisms; Studies; Sweden; Sweden; United States
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2742

Patrick Sullivan and colleagues report a multi-stage genome-wide association study for schizophrenia in a Swedish population. They identify 13 loci newly associated with schizophrenia. 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.