Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis

被引：33

作者：

Chung, Sharon A. ^{[3
]}

Xie, Gang ^{[2
]}

Roshandel, Delnaz ^{[2
]}

Sherva, Richard ^{[1
]}

Edberg, Jeffrey C. ^{[4
]}

Kravitz, Megan ^{[1
]}

Dellaripa, Paul F. ^{[5
]}

Hoffman, Gary S. ^{[6
]}

Mahr, Alfred D. ^{[1
,7
,8
]}

Seo, Philip ^{[9
]}

Specks, Ulrich ^{[10
]}

Spiera, Robert F. ^{[11
]}

St Clair, E. William ^{[12
]}

Stone, John H. ^{[13
]}

Plenge, Robert M. ^{[5
]}

Siminovitch, Katherine A. ^{[2
]}

Merkel, Peter A. ^{[1
]}

Monach, Paul A. ^{[1
]}

机构：

[1] Boston Univ, Sch Med, Boston, MA 02118 USA

[2] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada

[3] Univ San Francisco, San Francisco, CA 94117 USA

[4] Univ Alabama Birmingham, Birmingham, AL USA

[5] Brigham & Womens Hosp, Boston, MA 02115 USA

[6] Cleveland Clin, Cleveland, OH 44106 USA

[7] Univ Paris 07, Paris, France

[8] Hop St Louis, AP HP, Paris, France

[9] Johns Hopkins Univ, Baltimore, MD USA

[10] Mayo Clin, Coll Med, Rochester, MN USA

[11] Hosp Special Surg, New York, NY 10021 USA

[12] Duke Univ, Durham, NC USA

[13] Massachusetts Gen Hosp, Boston, MA 02114 USA

来源：

ARTHRITIS AND RHEUMATISM | 2012年 / 64卷 / 10期

关键词：

GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SINGLE-NUCLEOTIDE POLYMORPHISMS; COLITIS-RISK LOCI; ULCERATIVE-COLITIS; AUTOIMMUNE-DISEASES; MULTIPLE-SCLEROSIS; COMMON VARIANTS; REPLICATION; PTPN22;

D O I：

10.1002/art.34496

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (Wegener's) (GPA), and to determine whether the genetic susceptibility profiles of other autoimmune diseases are associated with those of GPA. Methods Genetic data from 2 cohorts were meta-analyzed. Genotypes for 168 previously identified single-nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained in a total of 880 patients with GPA and 1,969 control subjects of European descent. Single-marker associations were identified using additive logistic regression models. Associations of multiple SNPs with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn's disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis (RA), celiac disease, and ulcerative colitis. Adjustment for population substructure was performed in all analyses, using ancestry-informative markers and principal components analysis. Results Genetic polymorphisms in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (odds ratio [OR] 0.79, 95% confidence interval [95% CI] 0.700.89, P = 9.8 x 10-5). The genetic risk score for RA susceptibility markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score, 95% CI 1.021.08, P = 5.1 x 10-5). Conclusion RA and GPA may arise from a similar genetic predisposition. Aside from CTLA4, other loci previously found to be associated with common autoimmune diseases were not statistically significantly associated with GPA in this study.

引用

页码：3463 / 3471

页数：9

共 70 条

[1] Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47 [J].

Anderson, Carl A. ;

Boucher, Gabrielle ;

Lees, Charlie W. ;

Franke, Andre ;

D'Amato, Mauro ;

Taylor, Kent D. ;

Lee, James C. ;

Goyette, Philippe ;

Imielinski, Marcin ;

Latiano, Anna ;

Lagace, Caroline ;

Scott, Regan ;

Amininejad, Leila ;

Bumpstead, Suzannah ;

Baidoo, Leonard ;

Baldassano, Robert N. ;

Barclay, Murray ;

Bayless, Theodore M. ;

Brand, Stephan ;

Buening, Carsten ;

Colombel, Jean-Frederic ;

Denson, Lee A. ;

De Vos, Martine ;

Dubinsky, Marla ;

Edwards, Cathryn ;

Ellinghaus, David ;

Fehrmann, Rudolf S. N. ;

Floyd, James A. B. ;

Florin, Timothy ;

Franchimont, Denis ;

Franke, Lude ;

Georges, Michel ;

Glas, Juergen ;

Glazer, Nicole L. ;

Guthery, Stephen L. ;

Haritunians, Talin ;

Hayward, Nicholas K. ;

Hugot, Jean-Pierre ;

Jobin, Gilles ;

Laukens, Debby ;

Lawrance, Ian ;

Lemann, Marc ;

Levine, Arie ;

Libioulle, Cecile ;

Louis, Edouard ;

McGovern, Dermot P. ;

Milla, Monica ;

Montgomery, Grant W. ;

Morley, Katherine I. ;

Mowat, Craig .

NATURE GENETICS, 2011, 43 (03) :246-U94

[2] Investigation of Crohn's Disease Risk Loci in Ulcerative Colitis Further Defines Their Molecular Relationship [J].

Anderson, Carl A. ;

Massey, Dunecan C. O. ;

Barrett, Jeffrey C. ;

Prescott, Natalie J. ;

Tremelling, Mark ;

Fisher, Sheila A. ;

Gwilliam, Rhian ;

Jacob, Jemima ;

Nimmo, Elaine R. ;

Drummond, Hazel ;

Lees, Charlie W. ;

Onnie, Clive M. ;

Hanson, Catherine ;

Blaszczyk, Katarzyna ;

Ravindrarajah, Radhi ;

Hunt, Sarah ;

Varma, Dhiraj ;

Hammond, Naomi ;

Lewis, Gregory ;

Attlesey, Heather ;

Watkins, Nick ;

Ouwehand, Willem ;

Strachan, David ;

McArdle, Wendy ;

Lewis, Cathryn M. ;

Lobo, Alan ;

Sanderson, Jeremy ;

Jewell, Derek P. ;

Deloukas, Panos ;

Mansfield, John C. ;

Mathew, Christopher G. ;

Satsangi, Jack ;

Parkes, Miles .

GASTROENTEROLOGY, 2009, 136 (02) :523-529

[3] 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

[4] Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region [J].

Barrett, Jeffrey C. ;

Lee, James C. ;

Lees, Charles W. ;

Prescott, Natalie J. ;

Anderson, Carl A. ;

Phillips, Anne ;

Wesley, Emma ;

Parnell, Kirstie ;

Zhang, Hu ;

Drummond, Hazel ;

Nimmo, Elaine R. ;

Massey, Dunecan ;

Blaszczyk, Kasia ;

Elliott, Timothy ;

Cotterill, Lynn ;

Dallal, Helen ;

Lobo, Alan J. ;

Mowat, Craig ;

Sanderson, Jeremy D. ;

Jewell, Derek P. ;

Newman, William G. ;

Edwards, Cathryn ;

Ahmad, Tariq ;

Mansfield, John C. ;

Satsangi, Jack ;

Parkes, Miles ;

Mathew, Christopher G. ;

Donnelly, Peter ;

Peltonen, Leena ;

Blackwell, Jenefer M. ;

Bramon, Elvira ;

Brown, Matthew A. ;

Casas, Juan P. ;

Corvin, Aiden ;

Craddock, Nicholas ;

Deloukas, Panos ;

Duncanson, Audrey ;

Jankowski, Janusz ;

Markus, Hugh S. ;

McCarthy, Mark I. ;

Palmer, Colin N. A. ;

Plomin, Robert ;

Rautanen, Anna ;

Sawcer, Stephen J. ;

Samani, Nilesh ;

Trembath, Richard C. ;

Viswanathan, Ananth C. ;

Wood, Nicholas ;

Spencer, Chris C. A. ;

Bellenguez, Celine .

NATURE GENETICS, 2009, 41 (12) :1330-U99

[5] 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

[6] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[7] Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis [J].

Capon, Francesca ;

Di Meglio, Paola ;

Szaub, Joanna ;

Prescott, Natalie J. ;

Dunster, Christina ;

Baumber, Laura ;

Gutin, Alexander ;

Abkevic, Victor ;

Burden, A. David ;

Lanchbury, Jerry ;

Barker, Jonathan N. ;

Trembath, Richard C. ;

Nestle, Frank O. .

HUMAN GENETICS, 2007, 122 (02) :201-206

[8] Contrasting genetic association of IL2RA with SLE and ANCA - associated vasculitis [J].

Carr, Edward J. ;

Clatworthy, Menna R. ;

Lowe, Christopher E. ;

Todd, John A. ;

Wong, Andrew ;

Vyse, Timothy J. ;

Kamesh, Lavanya ;

Watts, Richard A. ;

Lyons, Paul A. ;

Smith, Kenneth G. C. .

BMC MEDICAL GENETICS, 2009, 10

[9]

Choi HK, 2001, J RHEUMATOL, V28, P1584

[10] Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci [J].

Cooper, Jason D. ;

Smyth, Deborah J. ;

Smiles, Adam M. ;

Plagnol, Vincent ;

Walker, Neil M. ;

Allen, James E. ;

Downes, Kate ;

Barrett, Jeffrey C. ;

Healy, Barry C. ;

Mychaleckyj, Josyf C. ;

Warram, James H. ;

Todd, John A. .

NATURE GENETICS, 2008, 40 (12) :1399-1401

← 1 2 3 4 5 6 7 →