Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)748-752
Number of pages5
JournalNature
Volume460
Issue number7256
DOIs
Publication statusPublished - 6 Aug 2009

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