Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

被引：3488

作者：

Purcell, Shaun M. ^{[1
,2
,3
,4
]}

Wray, Naomi R. ^{[5
]}

Stone, Jennifer L. ^{[1
,2
,3
,4
]}

Visscher, Peter M. ^{[5
]}

O'Donovan, Michael C. ^{[6
]}

Sullivan, Patrick F. ^{[7
,8
]}

Sklar, Pamela ^{[1
,2
,3
,4
]}

Ruderfer, Douglas M. ^{[1
,2
,3
,4
]}

McQuillin, Andrew ^{[9
]}

Morris, Derek W. ^{[10
,11
]}

O'Dushlaine, Colm T. ^{[10
,11
]}

Corvin, Aiden ^{[10
,11
]}

Holmans, Peter A. ^{[6
]}

Macgregor, Stuart ^{[5
]}

Gurling, Hugh ^{[9
]}

Blackwood, Douglas H. R. ^{[12
]}

Craddock, Nick J. ^{[6
]}

Gill, Michael ^{[10
,11
]}

Hultman, Christina M. ^{[13
,14
]}

Kirov, George K. ^{[6
]}

Lichtenstein, Paul ^{[13
]}

Muir, Walter J. ^{[12
]}

Owen, Michael J. ^{[6
]}

Pato, Carlos N. ^{[15
]}

Scolnick, Edward M. ^{[2
,3
]}

St Clair, David ^{[16
]}

Williams, Nigel M. ^{[6
]}

Georgieva, Lyudmila ^{[6
]}

Nikolov, Ivan ^{[6
]}

Norton, N. ^{[6
]}

Williams, H. ^{[6
]}

Toncheva, Draga ^{[18
]}

Milanova, Vihra ^{[19
]}

Thelander, Emma F. ^{[13
]}

Sullivan, Patrick ^{[7
,8
]}

Kenny, Elaine ^{[10
,11
]}

Quinn, Emma M. ^{[10
,11
]}

Choudhury, Khalid ^{[9
]}

Datta, Susmita ^{[9
]}

Pimm, Jonathan ^{[9
]}

Thirumalai, Srinivasa ^{[20
]}

Puri, Vinay ^{[9
]}

Krasucki, Robert ^{[9
]}

Lawrence, Jacob ^{[9
]}

Quested, Digby ^{[21
]}

Bass, Nicholas ^{[9
]}

Crombie, Caroline ^{[17
]}

Fraser, Gillian ^{[17
]}

Kuan, Soh Leh ^{[22
]}

Walker, Nicholas ^{[16
]}

机构：

[1] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[3] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[4] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[5] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[6] Cardiff Univ, Sch Med, Dept Psychol Med, MRC Ctr Neuropsychiat Genet & Gen, Cardiff C14 4XN, Wales

[7] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[8] Univ N Carolina, Dept Psychiat & Epidemiol, Chapel Hill, NC 27599 USA

[9] UCL, Sch Med, Mol Psychiat Lab, Res Dept Mental Hlth Sci,Windeyer Inst Med Sci, London W1T 4JF, England

[10] Univ Dublin Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland

[11] Univ Dublin Trinity Coll, Inst Mol Med, Dublin 2, Ireland

[12] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland

[13] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden

[14] Uppsala Univ, Dept Neurosci, SE-75017 Uppsala, Sweden

[15] Univ So Calif, Ctr Genom Psychiat, Los Angeles, CA 90033 USA

[16] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland

[17] Univ Aberdeen, Dept Mental Hlth, Aberdeen AB25 2ZD, Scotland

[18] Univ Hosp Maichin Dom, Dept Med Genet, Sofia 1431, Bulgaria

[19] Alexander Univ Hosp, Psychiat Clin 1, Dept Psychiat, Sofia 1431, Bulgaria

[20] W Berkshire NHS Trust, Reading RG3 5LR, Berks, England

[21] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England

[22] Ravenscraig Hosp, Greenock PA16 9HA, Scotland

[23] SUNY Syracuse, Upstate Med Univ Syracuse, Syracuse, NY 13210 USA

[24] Washington VA Med Ctr, Washington, DC 20422 USA

[25] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC 20057 USA

[26] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA

[27] Dept Psychiat, P-9500310 Sao Miguel, Azores, Portugal

[28] Univ Coimbra, Dept Psychiat, P-3004504 Coimbra, Portugal

来源：

NATURE | 2009年 / 460卷 / 7256期

基金：

英国医学研究理事会; 英国惠康基金; 爱尔兰科学基金会;

关键词：

GENOME-WIDE ASSOCIATION; MULTIPLE RARE ALLELES; PSYCHIATRIC-DISORDERS; DISEASE; GENES; LOCI; TWIN;

D O I：

10.1038/nature08185

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：748 / 752

页数：5

共 27 条

[1] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[2]

Cardno AG, 2000, AM J MED GENET, V97, P12, DOI 10.1002/(SICI)1096-8628(200021)97:1<12::AID-AJMG3>3.3.CO

[3]

2-L

[4] Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders [J].

Cichon, Sven ;

Craddock, Nick ;

Daly, Mark ;

Faraone, Stephen V. ;

Gejman, Pablo V. ;

Kelsoe, John ;

Lehner, Thomas ;

Levinson, Douglas F. ;

Moran, Audra ;

Sklar, Pamela ;

Sullivan, Patrick F. .

AMERICAN JOURNAL OF PSYCHIATRY, 2009, 166 (05) :540-556

[5] A framework for interpreting genome-wide association studies of psychiatric disorders The Psychiatric GWAS Consortium Steering Committee [J].

Cichon, Sven ;

Craddock, Nick ;

Daly, Mark ;

Faraone, Stephen V. ;

Gejman, Pablo V. ;

Kelsoe, John ;

Lehner, Thomas ;

Levinson, Douglas F. ;

Moran, Audra ;

Sklar, Pamela ;

Sullivan, Patrick F. .

MOLECULAR PSYCHIATRY, 2009, 14 (01) :10-17

[6] Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology [J].

Craddock, N ;

O'Donovan, MC ;

Owen, MJ .

SCHIZOPHRENIA BULLETIN, 2006, 32 (01) :9-16

[7] Phenotypic and genetic complexity of psychosis - Invited commentary on ... Schizophrenia: a common disease caused by multiple rare alleles [J].

Craddock, Nick ;

O'Donovan, Michael C. ;

Owen, Michael J. .

BRITISH JOURNAL OF PSYCHIATRY, 2007, 190 :200-203

[8]

FISHER RA, 1918, PHILOS T R SOC EDINB, V399, P433

[9] A POLYGENIC THEORY OF SCHIZOPHRENIA [J].

GOTTESMAN, II ;

SHIELDS, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1967, 58 (01) :199-+

[10] Variation analysis and gene annotation of eight MHC haplotypes: The MHC haplotype project [J].

Horton, Roger ;

Gibson, Richard ;

Coggill, Penny ;

Miretti, Marcos ;

Allcock, Richard J. ;

Almeida, Jeff ;

Forbes, Simon ;

Gilbert, James G. R. ;

Halls, Karen ;

Harrow, Jennifer L. ;

Hart, Elizabeth ;

Howe, Kevin ;

Jackson, David K. ;

Palmer, Sophie ;

Roberts, Anne N. ;

Sims, Sarah ;

Stewart, C. Andrew ;

Traherne, James A. ;

Trevanion, Steve ;

Wilming, Laurens ;

Rogers, Jane ;

de Jong, Pieter J. ;

Elliott, John F. ;

Sawcer, Stephen ;

Todd, John A. ;

Trowsdale, John ;

Beck, Stephan .

IMMUNOGENETICS, 2008, 60 (01) :1-18

← 1 2 3 →