Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

被引：1017

作者：

Stahl, Eli A. ^{[1
,2
]}

Raychaudhuri, Soumya ^{[1
,2
,3
]}

Remmers, Elaine F. ^{[4
]}

Xie, Gang ^{[5
,6
]}

Eyre, Stephen ^{[7
]}

Thomson, Brian P. ^{[2
]}

Li, Yonghong ^{[8
]}

Kurreeman, Fina A. S. ^{[1
,2
,9
]}

Zhernakova, Alexandra ^{[10
,11
]}

Hinks, Anne ^{[7
]}

Guiducci, Candace ^{[2
]}

Chen, Robert ^{[1
]}

Alfredsson, Lars ^{[12
]}

Amos, Christopher I. ^{[13
]}

Ardlie, Kristin G. ^{[2
]}

Barton, Anne ^{[7
]}

Bowes, John ^{[7
]}

Brouwer, Elisabeth ^{[11
,14
]}

Burtt, Noel P. ^{[2
]}

Catanese, Joseph J. ^{[8
]}

Coblyn, Jonathan ^{[1
]}

Coenen, Marieke J. H. ^{[15
]}

Costenbader, Karen H. ^{[1
]}

Criswell, Lindsey A. ^{[16
]}

Crusius, J. Bart A. ^{[17
]}

Cui, Jing ^{[1
]}

de Bakker, Paul I. W. ^{[2
,18
]}

De Jager, Philip L. ^{[2
,19
]}

Ding, Bo ^{[12
]}

Emery, Paul ^{[20
]}

Flynn, Edward ^{[7
]}

Harrison, Pille ^{[21
]}

Hocking, Lynne J. ^{[22
]}

Huizinga, Tom W. J. ^{[9
]}

Kastner, Daniel L. ^{[4
]}

Ke, Xiayi ^{[7
]}

Lee, Annette T. ^{[23
]}

Liu, Xiangdong ^{[5
,6
]}

Martin, Paul ^{[7
]}

Morgan, Ann W. ^{[20
]}

Padyukov, Leonid ^{[24
,25
]}

Posthumus, Marcel D. ^{[11
,14
]}

Radstake, Timothy R. D. J. ^{[26
]}

Reid, David M. ^{[22
]}

Seielstad, Mark ^{[27
]}

Seldin, Michael F. ^{[28
]}

Shadick, Nancy A. ^{[1
]}

Steer, Sophia ^{[29
]}

Tak, Paul P.

Thomson, Wendy ^{[7
]}

机构：

[1] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA

[2] Broad Inst, Cambridge, MA USA

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

[4] NIAMSD, Genet & Genom Branch, US NIH, Bethesda, MD 20892 USA

[5] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada

[6] Univ Hlth Network, Toronto, ON, Canada

[7] Univ Manchester, Arthrit Res UK Epidemiol Unit, Manchester, Lancs, England

[8] Celera, Alameda, CA USA

[9] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands

[10] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[11] Univ Groningen, Groningen, Netherlands

[12] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden

[13] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[14] Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, NL-9713 AV Groningen, Netherlands

[15] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[16] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA

[17] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Immunogenet Lab, Amsterdam, Netherlands

[18] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[19] Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA

[20] Univ Leeds, Leeds Inst Mol Med, Leeds Musculoskeletal Biomed Res Unit, Natl Inst Hlth Res, Leeds, W Yorkshire, England

[21] Univ Oxford, Inst Musculoskeletal Sci, Botnar Res Ctr, Oxford, England

[22] Univ Aberdeen, Div Appl Med, Musculoskeletal & Genet Sect, Aberdeen, Scotland

[23] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA

[24] Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden

[25] Karolinska Univ Hosp Solna, Stockholm, Sweden

[26] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands

[27] Genome Inst Singapore, Singapore, Singapore

[28] Univ Calif Davis, Rowe Program Genet, Davis, CA 95616 USA

[29] Kings Coll Hosp Natl Hlth Serv Fdn Trust, Clin & Acad Rheumatol, London, England

[30] Univ Amsterdam, Acad Med Ctr, Sanquin Res Landsteiner Lab, NL-1105 AZ Amsterdam, Netherlands

[31] Vrije Univ Amsterdam, Univ Med Ctr, Dept Rheumatol, Amsterdam, Netherlands

[32] Univ Sheffield, Sch Med & Biomed Sci, Sheffield, S Yorkshire, England

[33] Jan van Breemen Inst, Amsterdam, Netherlands

[34] Roche Diagnost, Pleasanton, CA USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 06期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUSCEPTIBILITY LOCI; CELIAC-DISEASE; VARIANTS; GENE; COMMON; REGION; POLYMORPHISMS; CONFIRMATION; REPLICATION;

D O I：

10.1038/ng.582

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.

引用

页码：508 / U56

页数：9

共 58 条

[1] THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].

ARNETT, FC ;

EDWORTHY, SM ;

BLOCH, DA ;

MCSHANE, DJ ;

FRIES, JF ;

COOPER, NS ;

HEALEY, LA ;

KAPLAN, SR ;

LIANG, MH ;

LUTHRA, HS ;

MEDSGER, TA ;

MITCHELL, DM ;

NEUSTADT, DH ;

PINALS, RS ;

SCHALLER, JG ;

SHARP, JT ;

WILDER, RL ;

HUNDER, GG .

ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324

[2] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[3] Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes [J].

Barrett, Jeffrey C. ;

Clayton, David G. ;

Concannon, Patrick ;

Akolkar, Beena ;

Cooper, Jason D. ;

Erlich, Henry A. ;

Julier, Cecile ;

Morahan, Grant ;

Nerup, Jorn ;

Nierras, Concepcion ;

Plagnol, Vincent ;

Pociot, Flemming ;

Schuilenburg, Helen ;

Smyth, Deborah J. ;

Stevens, Helen ;

Todd, John A. ;

Walker, Neil M. ;

Rich, Stephen S. .

NATURE GENETICS, 2009, 41 (06) :703-707

[4] Rheumatoid arthritis susceptibility loci at chromosomes 10p15, 12q13 and 22q13 [J].

Barton, Anne ;

Thomson, Wendy ;

Ke, Xiayi ;

Eyre, Steve ;

Hinks, Anne ;

Bowes, John ;

Plant, Darren ;

Gibbons, Laura J. ;

Wilson, Anthony G. ;

Bax, Deborah E. ;

Morgan, Ann W. ;

Emery, Paul ;

Steer, Sophia ;

Hocking, Lynne ;

Reid, David M. ;

Wordsworth, Paul ;

Harrison, Pille ;

Worthington, Jane .

NATURE GENETICS, 2008, 40 (10) :1156-1159

[5] Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis susceptibility locus and confirmation of two further pan-autoimmune susceptibility genes [J].

Barton, Anne ;

Eyre, Steve ;

Ke, Xiayi ;

Hinks, Anne ;

Bowes, John ;

Flynn, Edward ;

Martin, Paul ;

Wilson, Anthony G. ;

Morgan, Ann W. ;

Emery, Paul ;

Steer, Sophia ;

Hocking, Lynne J. ;

Reid, David M. ;

Harrison, Pille ;

Wordsworth, Paul ;

Thomson, Wendy ;

Worthington, Jane .

HUMAN MOLECULAR GENETICS, 2009, 18 (13) :2518-2522

[6] A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis [J].

Begovich, AB ;

Carlton, VEH ;

Honigberg, LA ;

Schrodi, SJ ;

Chokkalingam, AP ;

Alexander, HC ;

Ardlie, KG ;

Huang, QQ ;

Smith, AM ;

Spoerke, JM ;

Conn, MT ;

Chang, M ;

Chang, SYP ;

Saiki, RK ;

Catanese, JJ ;

Leong, DU ;

Garcia, VE ;

McAllister, LB ;

Jeffery, DA ;

Lee, AT ;

Batliwalla, F ;

Remmers, E ;

Criswell, LA ;

Seldin, MF ;

Kastner, DL ;

Amos, CI ;

Sninsky, JJ ;

Gregersen, PK .

AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (02) :330-337

[7] 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

[8] Common and different genetic background for rheumatoid arthritis and coeliac disease [J].

Coenen, Marieke J. H. ;

Trynka, Gosia ;

Heskamp, Sandra ;

Franke, Barbara ;

van Diemen, Cleo C. ;

Smolonska, Joanna ;

van Leeuwen, Miek ;

Brouwer, Elisabeth ;

Boezen, Marike H. ;

Postma, Dirkje S. ;

Platteel, Mathieu ;

Zanen, Pieter ;

Lammers, Jan-Willem W. J. ;

Groen, Harry J. M. ;

Mali, Willem P. T. M. ;

Mulder, Chris J. ;

Tack, Greetje J. ;

Verbeek, Wieke H. M. ;

Wolters, Victorien M. ;

Houwen, Roderick H. J. ;

Mearin, M. Luisa ;

van Heel, David A. ;

Radstake, Timothy R. D. J. ;

van Riel, Piet L. C. M. ;

Wijmenga, Cisca ;

Barrera, Pilar ;

Zhernakova, Alexandra .

HUMAN MOLECULAR GENETICS, 2009, 18 (21) :4195-4203

[9] Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies:: evidence of gene-environment interactions with heavy cigarette smoking [J].

Costenbader, Karen H. ;

Chang, Shun-Chiao ;

De Vivo, Immaculata ;

Plenge, Robert ;

Karlson, Elizabeth W. .

ARTHRITIS RESEARCH & THERAPY, 2008, 10 (03)

[10] Practical aspects of imputation-driven meta-analysis of genome-wide association studies [J].

de Bakker, Paul I. W. ;

Ferreira, Manuel A. R. ;

Jia, Xiaoming ;

Neale, Benjamin M. ;

Raychaudhuri, Soumya ;

Voight, Benjamin F. .

HUMAN MOLECULAR GENETICS, 2008, 17 :R122-R128

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