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; Douglas M. Ruderfer; Andrew McQuillin; Derek W. Morris; Colm T. Oĝdushlaine; Aiden Corvin; Peter A. Holmans; Michael C. Oĝdonovan; Stuart MacGregor; Hugh Gurling; Douglas H.R. Blackwood; Nick J. Craddock; Michael Gill; Christina M. Hultman; George K. Kirov; Paul Lichtenstein; Walter J. Muir; Michael J. Owen; Carlos N. Pato; Edward M. Scolnick; David St Clair; Nigel M. Williams; Lyudmila Georgieva; Ivan Nikolov; N. Norton; H. Williams; Draga Toncheva; Vihra Milanova; Emma F. Thelander; Colm T. O'Dushlaine; Elaine Kenny; Emma M. Quinn; 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; Kevin A. McGhee; Ben Pickard; Pat Malloy; Alan W. MacLean; Margaret Van Beck; 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; Pamela Sklar

doi:10.1038/nature08185

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
, Douglas M. Ruderfer
, Andrew McQuillin
, Derek W. Morris
, Colm T. Oĝdushlaine
, Aiden Corvin
, Peter A. Holmans
, Michael C. Oĝdonovan
, Stuart MacGregor
, Hugh Gurling
, Douglas H.R. Blackwood
, Nick J. Craddock
, Michael Gill
, Christina M. Hultman
, George K. Kirov

Paul Lichtenstein, Walter J. Muir, Michael J. Owen, Carlos N. Pato, Edward M. Scolnick, David St Clair, Nigel M. Williams, Lyudmila Georgieva, Ivan Nikolov, N. Norton, H. Williams, Draga Toncheva, Vihra Milanova, Emma F. Thelander, Colm T. O'Dushlaine, Elaine Kenny, Emma M. Quinn, 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, Kevin A. McGhee, Ben Pickard, Pat Malloy, Alan W. MacLean, Margaret Van Beck, 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, Pamela Sklar

Upstate Medical University

Massachusetts General Hospital
Broad Institute
Queensland Institute of Medical Research
Cardiff University
University of North Carolina at Chapel Hill
University College London
Trinity College Dublin
University of Edinburgh
Karolinska Institutet
Uppsala University
University of Southern California
Institute of Medical Sciences
Medical University Sofia
West Berkshire NHS Trust
University of Oxford
University of Aberdeen
Ravenscraig Hospital
VA Medical Center
Georgetown University
Virginia Commonwealth University
Department of Psychiatry
University of Coimbra

Research output: Contribution to journal › Article › peer-review

3945 Scopus citations

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
Pages (from-to)	748-752
Number of pages	5
Journal	Nature
Volume	460
Issue number	7256
DOIs	https://doi.org/10.1038/nature08185
State	Published - Aug 6 2009

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10.1038/nature08185

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Purcell, S. M., Wray, N. R., Stone, J. L., Visscher, P. M., O'Donovan, M. C., Sullivan, P. F., Ruderfer, D. M., McQuillin, A., Morris, D. W., Oĝdushlaine, C. T., Corvin, A., Holmans, P. A., Oĝdonovan, M. C., MacGregor, S., Gurling, H., Blackwood, D. H. R., Craddock, N. J., Gill, M., Hultman, C. M., ... Sklar, P. (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 460(7256), 748-752. https://doi.org/10.1038/nature08185

@article{fc239ab8b8a0426093a9021a6055d748,

title = "Common polygenic variation contributes to risk of schizophrenia and bipolar disorder",

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.",

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

year = "2009",

month = aug,

day = "6",

doi = "10.1038/nature08185",

language = "English",

volume = "460",

pages = "748--752",

journal = "Nature",

issn = "0028-0836",

number = "7256",

}

Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF, Ruderfer, DM, McQuillin, A, Morris, DW, Oĝdushlaine, CT, Corvin, A, Holmans, PA, Oĝdonovan, MC, MacGregor, S, Gurling, H, Blackwood, DHR, Craddock, NJ, Gill, M, Hultman, CM, Kirov, GK, Lichtenstein, P, Muir, WJ, Owen, MJ, Pato, CN, Scolnick, EM, St Clair, D, Williams, NM, Georgieva, L, Nikolov, I, Norton, N, Williams, H, Toncheva, D, Milanova, V, Thelander, EF, O'Dushlaine, CT, Kenny, E, Quinn, EM, Choudhury, K, Datta, S, Pimm, J, Thirumalai, S, Puri, V, Krasucki, R, Lawrence, J, Quested, D, Bass, N, Crombie, C, Fraser, G, Leh Kuan, S, Walker, N, McGhee, KA, Pickard, B, Malloy, P, MacLean, AW, Van Beck, M, Pato, MT, Medeiros, H, Middleton, F, Carvalho, C, Morley, C, Fanous, A, Conti, D, Knowles, JA, Paz Ferreira, C, MacEdo, A, Helena Azevedo, M, Kirby, AN, Ferreira, MAR, Daly, MJ, Chambert, K, Kuruvilla, F, Gabriel, SB, Ardlie, K, Moran, JL & Sklar, P 2009, 'Common polygenic variation contributes to risk of schizophrenia and bipolar disorder', Nature, vol. 460, no. 7256, pp. 748-752. https://doi.org/10.1038/nature08185

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

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 - https://www.scopus.com/pages/publications/68449086236

U2 - 10.1038/nature08185

DO - 10.1038/nature08185

M3 - Article

C2 - 19571811

SN - 0028-0836

VL - 460

SP - 748

EP - 752

JO - Nature

JF - Nature

IS - 7256

ER -

Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

Abstract

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