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 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; BIRAC Consortium, YEAR Consortium

doi: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 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, BIRAC Consortium, YEAR Consortium

Applied Medicine

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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)	508-514
Number of pages	7
Journal	Nature Genetics
Volume	42
Issue number	6
DOIs	https://doi.org/10.1038/ng.582
Publication status	Published - Jun 2010

Keywords

systemic-lupus-erythematosus
susceptibility loci
celiac-disease
variants
gene
common
region
polymorphisms
confirmation
replication

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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., ... BIRAC Consortium, YEAR Consortium (2010). Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nature Genetics, 42(6), 508-514. https://doi.org/10.1038/ng.582

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, L, 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 & BIRAC Consortium, YEAR Consortium 2010, 'Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci', Nature Genetics, vol. 42, no. 6, pp. 508-514. https://doi.org/10.1038/ng.582

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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.",

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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 Lynne Hocking 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 {BIRAC Consortium, YEAR Consortium}",

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AU - Stahl, Eli A.

AU - Raychaudhuri, Soumya

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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

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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

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 - BIRAC Consortium, YEAR Consortium

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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.

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KW - systemic-lupus-erythematosus

KW - susceptibility loci

KW - celiac-disease

KW - variants

KW - gene

KW - common

KW - region

KW - polymorphisms

KW - confirmation

KW - replication

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DO - 10.1038/ng.582

M3 - Article

SN - 1061-4036

VL - 42

SP - 508

EP - 514

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

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

Abstract

Keywords

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