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Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

Purcell, Shaun M., Wray, Naomi R., Stone, Jennifer L., Visscher, Peter M., O'Donovan, Michael Conlon ORCID:, Sullivan, Patrick F., Sklar, Pamela, Ruderfer, Douglas M., McQuillin, Andrew, Morris, Derek W., O'Dushlaine, Colm T., Corvin, Aiden, Holmans, Peter Alan ORCID:, Macgregor, Stuart, Gurling, Hugh, Blackwood, Douglas H. R., Craddock, Nicholas John ORCID:, Gill, Michael, Hultman, Christina M., Kirov, George ORCID:, Lichtenstein, Paul, Muir, Walter J., Owen, Michael John ORCID:, Pato, Carlos N., Scolnick, Edward M., St Clair, David, Williams, Nigel Melville ORCID:, Georgieva, Lyudmila, Nikolov, Ivan, Norton, Nadine ORCID:, Williams, Hywel John ORCID:, Toncheva, Draga, Milanova, Vihra, Thelander, Emma F., Kenny, Elaine, Quinn, Emma M., Choudhury, Khalid, Datta, Susmita, Pimm, Jonathan, Thirumalai, Srinivasa, Puri, Vinay, Krasucki, Robert, Lawrence, Jacob, Quested, Digby, Bass, Nicholas, Crombie, Caroline, Fraser, Gillian, Leh Kuan, Soh, Walker, Nicholas, McGhee, Kevin A., Pickard, Ben, Malloy, Pat, Maclean, Alan W., Van Beck, Margaret, Pato, Michele T., Medeiros, Helena, Middleton, Frank, Carvalho, Celia, Morley, Christopher, Fanous, Ayman, Conti, David, Knowles, James A., Paz Ferreira, Carlos, Macedo, Antonio, Helena Azevedo, M., Kirby, Andrew N., Ferreira, Manuel A. R., Daly, Mark J., Chambert, Kimberly, Kuruvilla, Finny, Gabriel, Stacey B., Ardlie, Kristin, Moran, Jennifer L. and Daly, Mark J. 2009. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460 (7256) , pp. 748-752. 10.1038/nature08185

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Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%1, 2. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Additional Information: Authors are members of The International Schizophrenia Consortium
Publisher: Nature Publishing Group
ISSN: 0028-0836
Last Modified: 07 Nov 2022 07:50

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