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

Eli A. Stahl; Soumya Raychaudhuri; Elaine F. Remmers; Gang Xie; Stephen Eyre; Brian P. Thomson; Yonghong Li; Fina A. S. Kurreeman; Alexandra Zhernakova; Anne Hinks; Candace Guiducci; Robert Chen; Lars Alfredsson; Christopher I. Amos; Kristin G. Ardlie; Anne Barton; John Bowes; Elisabeth Brouwer; Noel P. Burtt; Joseph J. Catanese; Jonathan Coblyn; Marieke J. H. Coenen; Karen H. Costenbader; Lindsey A. Criswell; J. Bart A. Crusius; Jing Cui; Paul I. W. de Bakker; Philip L. de Jager; Bo Ding; Paul Emery; Edward Flynn; Pille Harrison; Lynne J. Hocking; Tom W. J. Huizinga; Daniel L. Kastner; Xiayi Ke; Annette T. Lee; Xiangdong Liu; Paul Martin; Ann W. Morgan; Leonid Padyukov; Marcel D. Posthumus; Timothy R. D. J. Radstake; David M. Reid; Mark Seielstad; Michael F. Seldin; Nancy A. Shadick; Sophia Steer; Paul P. Tak; Wendy Thomson; Annette H. M. van der Helm-van Mil; Irene E. van der Horst-Bruinsma; C. Ellen van der Schoot; Piet L. C. M. van Riel; Michael E. Weinblatt; Anthony G. Wilson; Gert Jan Wolbink; B. Paul Wordsworth; Cisca Wijmenga; Elizabeth W. Karlson; Rene E. M. Toes; Niek de Vries; Ann B. Begovich; Jane Worthington; Katherine A. Siminovitch; Peter K. Gregersen; Lars Klareskog; Robert M. Plenge

doi:https://doi.org/10.1038/ng.582

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

Eli A. Stahl, Soumya Raychaudhuri, Elaine F. Remmers, Gang Xie, Stephen Eyre, Brian P. Thomson, Yonghong Li, Fina A. S. Kurreeman, Alexandra Zhernakova, Anne Hinks, Candace Guiducci, Robert Chen, Lars Alfredsson, Christopher I. Amos, Kristin G. Ardlie, Anne Barton, John Bowes, Elisabeth Brouwer, Noel P. Burtt, Joseph J. CataneseJonathan Coblyn, Marieke J. H. Coenen, Karen H. Costenbader, Lindsey A. Criswell, J. Bart A. Crusius, Jing Cui, Paul I. W. de Bakker, Philip L. de Jager, Bo Ding, Paul Emery, Edward Flynn, Pille Harrison, Lynne J. Hocking, Tom W. J. Huizinga, Daniel L. Kastner, Xiayi Ke, Annette T. Lee, Xiangdong Liu, Paul Martin, Ann W. Morgan, Leonid Padyukov, Marcel D. Posthumus, Timothy R. D. J. Radstake, David M. Reid, Mark Seielstad, Michael F. Seldin, Nancy A. Shadick, Sophia Steer, Paul P. Tak, Wendy Thomson, Annette H. M. van der Helm-van Mil, Irene E. van der Horst-Bruinsma, C. Ellen van der Schoot, Piet L. C. M. van Riel, Michael E. Weinblatt, Anthony G. Wilson, Gert Jan Wolbink, B. Paul Wordsworth, Cisca Wijmenga, Elizabeth W. Karlson, Rene E. M. Toes, Niek de Vries, Ann B. Begovich, Jane Worthington, Katherine A. Siminovitch, Peter K. Gregersen, Lars Klareskog, Robert M. Plenge

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Abstract

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

Original language	English
Pages (from-to)	508-U56
Journal	Nature Genetics
Volume	42
Issue number	6
DOIs	https://doi.org/10.1038/ng.582
Publication status	Published - 2010

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Stahl, E. A., Raychaudhuri, S., Remmers, E. F., Xie, G., Eyre, S., Thomson, B. P., Li, Y., Kurreeman, F. A. S., Zhernakova, A., Hinks, A., Guiducci, C., Chen, R., Alfredsson, L., Amos, C. I., Ardlie, K. G., Barton, A., Bowes, J., Brouwer, E., Burtt, N. P., ... Plenge, R. M. (2010). Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nature Genetics, 42(6), 508-U56. https://doi.org/10.1038/ng.582

@article{e514eab455284b968bd194195064fdd8,

title = "Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci",

abstract = "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",

author = "Stahl, {Eli A.} and Soumya Raychaudhuri and Remmers, {Elaine F.} and Gang Xie and Stephen Eyre and Thomson, {Brian P.} and Yonghong Li and Kurreeman, {Fina A. S.} and Alexandra Zhernakova and Anne Hinks and Candace Guiducci and Robert Chen and Lars Alfredsson and Amos, {Christopher I.} and Ardlie, {Kristin G.} and Anne Barton and John Bowes and Elisabeth Brouwer and Burtt, {Noel P.} and Catanese, {Joseph J.} and Jonathan Coblyn and Coenen, {Marieke J. H.} and Costenbader, {Karen H.} and Criswell, {Lindsey A.} and Crusius, {J. Bart A.} and Jing Cui and {de Bakker}, {Paul I. W.} and {de Jager}, {Philip L.} and Bo Ding and Paul Emery and Edward Flynn and Pille Harrison and Hocking, {Lynne J.} and Huizinga, {Tom W. J.} and Kastner, {Daniel L.} and Xiayi Ke and Lee, {Annette T.} and Xiangdong Liu and Paul Martin and Morgan, {Ann W.} and Leonid Padyukov and Posthumus, {Marcel D.} and Radstake, {Timothy R. D. J.} and Reid, {David M.} and Mark Seielstad and Seldin, {Michael F.} and Shadick, {Nancy A.} and Sophia Steer and Tak, {Paul P.} and Wendy Thomson and {van der Helm-van Mil}, {Annette H. M.} and {van der Horst-Bruinsma}, {Irene E.} and {van der Schoot}, {C. Ellen} and {van Riel}, {Piet L. C. M.} and Weinblatt, {Michael E.} and Wilson, {Anthony G.} and Wolbink, {Gert Jan} and Wordsworth, {B. Paul} and Cisca Wijmenga and Karlson, {Elizabeth W.} and Toes, {Rene E. M.} and {de Vries}, Niek and Begovich, {Ann B.} and Jane Worthington and Siminovitch, {Katherine A.} and Gregersen, {Peter K.} and Lars Klareskog and Plenge, {Robert M.}",

year = "2010",

doi = "https://doi.org/10.1038/ng.582",

language = "English",

volume = "42",

pages = "508--U56",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

Stahl, EA, Raychaudhuri, S, Remmers, EF, Xie, G, Eyre, S, Thomson, BP, Li, Y, Kurreeman, FAS, Zhernakova, A, Hinks, A, Guiducci, C, Chen, R, Alfredsson, L, Amos, CI, Ardlie, KG, Barton, A, Bowes, J, Brouwer, E, Burtt, NP, Catanese, JJ, Coblyn, J, Coenen, MJH, Costenbader, KH, Criswell, LA, Crusius, JBA, Cui, J, de Bakker, PIW, de Jager, PL, Ding, B, Emery, P, Flynn, E, Harrison, P, Hocking, LJ, Huizinga, TWJ, Kastner, DL, Ke, X, Lee, AT, Liu, X, Martin, P, Morgan, AW, Padyukov, L, Posthumus, MD, Radstake, TRDJ, Reid, DM, Seielstad, M, Seldin, MF, Shadick, NA, Steer, S, Tak, PP, Thomson, W, van der Helm-van Mil, AHM, van der Horst-Bruinsma, IE , van der Schoot, CE, van Riel, PLCM, Weinblatt, ME, Wilson, AG, Wolbink, GJ, Wordsworth, BP, Wijmenga, C, Karlson, EW, Toes, REM, de Vries, N, Begovich, AB, Worthington, J, Siminovitch, KA, Gregersen, PK, Klareskog, L & Plenge, RM 2010, 'Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci', Nature Genetics, vol. 42, no. 6, pp. 508-U56. https://doi.org/10.1038/ng.582

TY - JOUR

T1 - Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

AU - Stahl, Eli A.

AU - Raychaudhuri, Soumya

AU - Remmers, Elaine F.

AU - Xie, Gang

AU - Eyre, Stephen

AU - Thomson, Brian P.

AU - Li, Yonghong

AU - Kurreeman, Fina A. S.

AU - Zhernakova, Alexandra

AU - Hinks, Anne

AU - Guiducci, Candace

AU - Chen, Robert

AU - Alfredsson, Lars

AU - Amos, Christopher I.

AU - Ardlie, Kristin G.

AU - Barton, Anne

AU - Bowes, John

AU - Brouwer, Elisabeth

AU - Burtt, Noel P.

AU - Catanese, Joseph J.

AU - Coblyn, Jonathan

AU - Coenen, Marieke J. H.

AU - Costenbader, Karen H.

AU - Criswell, Lindsey A.

AU - Crusius, J. Bart A.

AU - Cui, Jing

AU - de Bakker, Paul I. W.

AU - de Jager, Philip L.

AU - Ding, Bo

AU - Emery, Paul

AU - Flynn, Edward

AU - Harrison, Pille

AU - Hocking, Lynne J.

AU - Huizinga, Tom W. J.

AU - Kastner, Daniel L.

AU - Ke, Xiayi

AU - Lee, Annette T.

AU - Liu, Xiangdong

AU - Martin, Paul

AU - Morgan, Ann W.

AU - Padyukov, Leonid

AU - Posthumus, Marcel D.

AU - Radstake, Timothy R. D. J.

AU - Reid, David M.

AU - Seielstad, Mark

AU - Seldin, Michael F.

AU - Shadick, Nancy A.

AU - Steer, Sophia

AU - Tak, Paul P.

AU - Thomson, Wendy

AU - van der Helm-van Mil, Annette H. M.

AU - van der Horst-Bruinsma, Irene E.

AU - van der Schoot, C. Ellen

AU - van Riel, Piet L. C. M.

AU - Weinblatt, Michael E.

AU - Wilson, Anthony G.

AU - Wolbink, Gert Jan

AU - Wordsworth, B. Paul

AU - Wijmenga, Cisca

AU - Karlson, Elizabeth W.

AU - Toes, Rene E. M.

AU - de Vries, Niek

AU - Begovich, Ann B.

AU - Worthington, Jane

AU - Siminovitch, Katherine A.

AU - Gregersen, Peter K.

AU - Klareskog, Lars

AU - Plenge, Robert M.

PY - 2010

Y1 - 2010

N2 - 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

AB - 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

U2 - https://doi.org/10.1038/ng.582

DO - https://doi.org/10.1038/ng.582

M3 - Article

C2 - 20453842

SN - 1061-4036

VL - 42

SP - 508-U56

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -