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

Stephan Ripke, Colm O'Dushlaine, Kimberly Chambert, Jennifer L Moran, Anna K Kähler, Susanne Akterin, Sarah E Bergen, Ann L Collins, James J Crowley, Menachem Fromer, Yunjung Kim, Sang Hong Lee, Patrik K E Magnusson, Nick Sanchez, Eli A Stahl, Stephanie Williams, Naomi R Wray, Kai Xia, Francesco Bettella, Anders D BorglumBrendan K Bulik-Sullivan, Paul Cormican, Nick Craddock, Christiaan de Leeuw, Naser Durmishi, Michael Gill, Vera Golimbet, Marian L Hamshere, Peter Holmans, David M Hougaard, Kenneth S Kendler, Kuang Lin, Derek W Morris, Ole Mors, Preben B Mortensen, Benjamin M Neale, Francis A O'Neill, Michael J Owen, Milica Pejovic Milovancevic, Danielle Posthuma, John Powell, Alexander L Richards, Brien P Riley, Douglas Ruderfer, Dan Rujescu, Engilbert Sigurdsson, Teimuraz Silagadze, August B Smit, Hreinn Stefansson, Francis A O'Neill, Multicenter Genetic Studies of Schizophrenia Consortium

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932 Citations (Scopus)

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 languageEnglish
Pages (from-to)1150-1159
JournalNature Genetics
Volume45
DOIs
Publication statusPublished - 25 Aug 2013

Bibliographical note

This is the second large study using Genome-Wide Association using data from the ICCSS and the RPGI sample to uncover genes for schizophrenia. These two samples together with other worldwide samples were used to find 13new loci for schizophrenia. This represents a significant breakthrough in understanding some of the mechanisms underlying risk for schizophrenia. I helped write the grants that helped with the collection of the data,I contributed towards the analysis and the write up of the paper.

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    Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., Collins, A. L., Crowley, J. J., Fromer, M., Kim, Y., Lee, S. H., Magnusson, P. K. E., Sanchez, N., Stahl, E. A., Williams, S., Wray, N. R., Xia, K., Bettella, F., ... Multicenter Genetic Studies of Schizophrenia Consortium (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45, 1150-1159. https://doi.org/10.1038/ng.2742