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%. 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 language | English (US) |
|---|---|
| Pages (from-to) | 748-752 |
| Number of pages | 5 |
| Journal | Nature |
| Volume | 460 |
| Issue number | 7256 |
| DOIs | |
| State | Published - Aug 6 2009 |
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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 C.; Sullivan, Patrick F.; Ruderfer, Douglas M.; McQuillin, Andrew; Morris, Derek W.; Oĝdushlaine, Colm T.; Corvin, Aiden; Holmans, Peter A.; Oĝdonovan, Michael C.; MacGregor, Stuart; Gurling, Hugh; Blackwood, Douglas H.R.; Craddock, Nick J.; Gill, Michael; Hultman, Christina M.; Kirov, George K.; Lichtenstein, Paul; Muir, Walter J.; Owen, Michael J.; Pato, Carlos N.; Scolnick, Edward M.; St Clair, David; Williams, Nigel M.; Georgieva, Lyudmila; Nikolov, Ivan; Norton, N.; Williams, H.; Toncheva, Draga; Milanova, Vihra; Thelander, Emma F.; O'Dushlaine, Colm T.; 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.; Sklar, Pamela.
In: Nature, Vol. 460, No. 7256, 06.08.2009, p. 748-752.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
AU - Purcell, Shaun M.
AU - Wray, Naomi R.
AU - Stone, Jennifer L.
AU - Visscher, Peter M.
AU - O'Donovan, Michael C.
AU - Sullivan, Patrick F.
AU - Ruderfer, Douglas M.
AU - McQuillin, Andrew
AU - Morris, Derek W.
AU - Oĝdushlaine, Colm T.
AU - Corvin, Aiden
AU - Holmans, Peter A.
AU - Oĝdonovan, Michael C.
AU - MacGregor, Stuart
AU - Gurling, Hugh
AU - Blackwood, Douglas H.R.
AU - Craddock, Nick J.
AU - Gill, Michael
AU - Hultman, Christina M.
AU - Kirov, George K.
AU - Lichtenstein, Paul
AU - Muir, Walter J.
AU - Owen, Michael J.
AU - Pato, Carlos N.
AU - Scolnick, Edward M.
AU - St Clair, David
AU - Williams, Nigel M.
AU - Georgieva, Lyudmila
AU - Nikolov, Ivan
AU - Norton, N.
AU - Williams, H.
AU - Toncheva, Draga
AU - Milanova, Vihra
AU - Thelander, Emma F.
AU - O'Dushlaine, Colm T.
AU - Kenny, Elaine
AU - Quinn, Emma M.
AU - Choudhury, Khalid
AU - Datta, Susmita
AU - Pimm, Jonathan
AU - Thirumalai, Srinivasa
AU - Puri, Vinay
AU - Krasucki, Robert
AU - Lawrence, Jacob
AU - Quested, Digby
AU - Bass, Nicholas
AU - Crombie, Caroline
AU - Fraser, Gillian
AU - Leh Kuan, Soh
AU - Walker, Nicholas
AU - McGhee, Kevin A.
AU - Pickard, Ben
AU - Malloy, Pat
AU - MacLean, Alan W.
AU - Van Beck, Margaret
AU - Pato, Michele T.
AU - Medeiros, Helena
AU - Middleton, Frank
AU - Carvalho, Celia
AU - Morley, Christopher
AU - Fanous, Ayman
AU - Conti, David
AU - Knowles, James A.
AU - Paz Ferreira, Carlos
AU - MacEdo, Antonio
AU - Helena Azevedo, M.
AU - Kirby, Andrew N.
AU - Ferreira, Manuel A.R.
AU - Daly, Mark J.
AU - Chambert, Kimberly
AU - Kuruvilla, Finny
AU - Gabriel, Stacey B.
AU - Ardlie, Kristin
AU - Moran, Jennifer L.
AU - Sklar, Pamela
N1 - Funding Information: Acknowledgements We thank the patients and families who contributed to these studies. We also thank E. Lander, N. Patterson and members of the Medical and Population Genetics group at the Broad Institute of Harvard and Massachusetts Institute of Technology for valuable discussion, and members of the Broad Biological Samples and Genetic Analysis Platforms for sample management and genotyping. We particularly thank D. Levinson and P. Gejman for allowing access to the MGS samples, and J. Shi for analytic support with the MGS samples. The group at the Stanley Center for Psychiatric Research at the Broad Institute was supported by the Stanley Medical Research Institute (E.M.S.), the Sylvan C. Herman Foundation (E.M.S.), and MH071681 (P.S.). The Cardiff University group was supported by a Medical Research Council (UK) Programme grant and the National Institutes of Mental Health (USA) (CONTE: 2 P50 MH066392-05A1). The group at the Karolinska Institutet was supported by the Swedish Council for Working Life and Social Research (FO 184/2000; 2001-2368). The Massachusetts General Hospital group was supported by the Stanley Medical Research Institute (P.S.), MH071681 and MH077139 (P.S.) and a Narsad Young Investigator Award (S.M.P.). The group at the Queensland Institute of Medical Research was supported by the Australian National Health and Medical Research Council (grants 389892, 442915, 496688 and 496674) and thanks S. Gordon for data preparation. The Trinity College Dublin group was supported by Science Foundation Ireland, the Health Research Board (Ireland), the Stanley Medical Research Institute and the Wellcome Trust; Irish controls were supplied by J. McPartlin from the Trinity College Biobank. The work at the University of Aberdeen was partly funded by GlaxoSmithKline and Generation Scotland, Genetics Health Initiative. University College London clinical and control samples were collected with support from the Neuroscience Research Charitable Trust, the Camden and Islington Mental Health and Social Care Trust, East London and City Mental Heath Trust, the West Berkshire NHS Trust, the West London Mental Health Trust, Oxfordshire and Buckinghamshire Mental Health Partnership NHS Trust, South Essex Partnership NHS Foundation Trust, Gloucestershire Partnership NHS Foundation Trust, Mersey Care NHS Trust, Hampshire Partnership NHS Trust and the North East London Mental Health Trust. The collection of the University of Edinburgh cohort was supported by the Wellcome Trust Clinical Research Facility (Edinburgh) and grants from The Wellcome Trust, London and the Chief Scientist Office of the Scottish Government. The group at the University of North Carolina, Chapel Hill, was supported by MH074027, MH077139 and MH080403, the Sylvan C. Herman Foundation (P.F.S.) and the Stanley Medical Research Institute (P.F.S.). The group at the University of Southern California thanks the patients and their families for their collaboration, and acknowledges the support of the National Institutes of Mental Health and the Department of Veterans Affairs.
PY - 2009/8/6
Y1 - 2009/8/6
N2 - 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%. 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.
AB - 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%. 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.
UR - http://www.scopus.com/inward/record.url?scp=68449086236&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68449086236&partnerID=8YFLogxK
U2 - 10.1038/nature08185
DO - 10.1038/nature08185
M3 - Article
C2 - 19571811
AN - SCOPUS:68449086236
VL - 460
SP - 748
EP - 752
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7256
ER -