Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk

Soumya Raychaudhuri; Brian P Thomson; Elaine F Remmers; Stephen Eyre; Anne Hinks; Candace Guiducci; Joseph J Catanese; Gang Xie; Eli A Stahl; Robert Chen; Lars Alfredsson; Christopher I Amos; Kristin G Ardlie; Anne Barton; John Bowes; Noel P Burtt; Monica Chang; Jonathan Coblyn; Karen H Costenbader; Lindsey A Criswell; J Bart A Crusius; Jing Cui; Phillip L De Jager; Bo Ding; Paul Emery; Edward Flynn; Pille Harrison; Lynne Hocking; Tom W J Huizinga; Daniel L Kastner; Xiayi Ke; Fina A S Kurreeman; Annette T Lee; Xiangdong Liu; Yonghong Li; Paul Martin; Ann W Morgan; Leonid Padyukov; 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; Michael E Weinblatt; Anthony G Wilson; Gert Jan Wolbink; BIRAC consortium

doi:10.1038/ng.479

Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk

Soumya Raychaudhuri, Brian P Thomson, Elaine F Remmers, Stephen Eyre, Anne Hinks, Candace Guiducci, Joseph J Catanese, Gang Xie, Eli A Stahl, Robert Chen, Lars Alfredsson, Christopher I Amos, Kristin G Ardlie, Anne Barton, John Bowes, Noel P Burtt, Monica Chang, Jonathan Coblyn, Karen H Costenbader, Lindsey A CriswellJ Bart A Crusius, Jing Cui, Phillip L De Jager, Bo Ding, Paul Emery, Edward Flynn, Pille Harrison, Lynne Hocking, Tom W J Huizinga, Daniel L Kastner, Xiayi Ke, Fina A S Kurreeman, Annette T Lee, Xiangdong Liu, Yonghong Li, Paul Martin, Ann W Morgan, Leonid Padyukov, 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, Michael E Weinblatt, Anthony G Wilson, Gert Jan Wolbink, BIRAC consortium

Applied Medicine

Research output: Contribution to journal › Letter › peer-review

294 Citations (Scopus)

Abstract

To discover new rheumatoid arthritis (RA) risk loci, we systematically examined 370 SNPs from 179 independent loci with P <0.001 in a published meta-analysis of RA genome-wide association studies (GWAS) of 3,393 cases and 12,462 controls. We used Gene Relationships Across Implicated Loci (GRAIL), a computational method that applies statistical text mining to PubMed abstracts, to score these 179 loci for functional relationships to genes in 16 established RA disease loci. We identified 22 loci with a significant degree of functional connectivity. We genotyped 22 representative SNPs in an independent set of 7,957 cases and 11,958 matched controls. Three were convincingly validated: CD2-CD58 (rs11586238, P = 1 x 10(-6) replication, P = 1 x 10(-9) overall), CD28 (rs1980422, P = 5 x 10(-6) replication, P = 1 x 10(-9) overall) and PRDM1 (rs548234, P = 1 x 10(-5) replication, P = 2 x 10(-8) overall). An additional four were replicated (P <0.0023): TAGAP (rs394581, P = 0.0002 replication, P = 4 x 10(-7) overall), PTPRC (rs10919563, P = 0.0003 replication, P = 7 x 10(-7) overall), TRAF6-RAG1 (rs540386, P = 0.0008 replication, P = 4 x 10(-6) overall) and FCGR2A (rs12746613, P = 0.0022 replication, P = 2 x 10(-5) overall). Many of these loci are also associated to other immunologic diseases.

Original language	English
Pages (from-to)	1313-1318
Number of pages	6
Journal	Nature Genetics
Volume	41
Issue number	12
Early online date	8 Nov 2009
DOIs	https://doi.org/10.1038/ng.479
Publication status	Published - Dec 2009

Keywords

antigens, CD2
antigens, CD28
antigens, CD58
arthritis, rheumatoid
case-control studies
genetic predisposition to disease
genetic Variation
genotype
humans
polymorphism, single nucleotide
repressor proteins
risk factors

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Raychaudhuri, S., Thomson, B. P., Remmers, E. F., Eyre, S., Hinks, A., Guiducci, C., Catanese, J. J., Xie, G., Stahl, E. A., Chen, R., Alfredsson, L., Amos, C. I., Ardlie, K. G., Barton, A., Bowes, J., Burtt, N. P., Chang, M., Coblyn, J., Costenbader, K. H., ... BIRAC consortium (2009). Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nature Genetics, 41(12), 1313-1318. https://doi.org/10.1038/ng.479

Raychaudhuri, S, Thomson, BP, Remmers, EF, Eyre, S, Hinks, A, Guiducci, C, Catanese, JJ, Xie, G, Stahl, EA, Chen, R, Alfredsson, L, Amos, CI, Ardlie, KG, Barton, A, Bowes, J, Burtt, NP, Chang, M, Coblyn, J, Costenbader, KH, Criswell, LA, Crusius, JBA, Cui, J, De Jager, PL, Ding, B, Emery, P, Flynn, E, Harrison, P, Hocking, L, Huizinga, TWJ, Kastner, DL, Ke, X, Kurreeman, FAS, Lee, AT, Liu, X, Li, Y, Martin, P, Morgan, AW, Padyukov, L, 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, Weinblatt, ME, Wilson, AG, Wolbink, GJ & BIRAC consortium 2009, 'Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk', Nature Genetics, vol. 41, no. 12, pp. 1313-1318. https://doi.org/10.1038/ng.479

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title = "Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk",

abstract = "To discover new rheumatoid arthritis (RA) risk loci, we systematically examined 370 SNPs from 179 independent loci with P <0.001 in a published meta-analysis of RA genome-wide association studies (GWAS) of 3,393 cases and 12,462 controls. We used Gene Relationships Across Implicated Loci (GRAIL), a computational method that applies statistical text mining to PubMed abstracts, to score these 179 loci for functional relationships to genes in 16 established RA disease loci. We identified 22 loci with a significant degree of functional connectivity. We genotyped 22 representative SNPs in an independent set of 7,957 cases and 11,958 matched controls. Three were convincingly validated: CD2-CD58 (rs11586238, P = 1 x 10(-6) replication, P = 1 x 10(-9) overall), CD28 (rs1980422, P = 5 x 10(-6) replication, P = 1 x 10(-9) overall) and PRDM1 (rs548234, P = 1 x 10(-5) replication, P = 2 x 10(-8) overall). An additional four were replicated (P <0.0023): TAGAP (rs394581, P = 0.0002 replication, P = 4 x 10(-7) overall), PTPRC (rs10919563, P = 0.0003 replication, P = 7 x 10(-7) overall), TRAF6-RAG1 (rs540386, P = 0.0008 replication, P = 4 x 10(-6) overall) and FCGR2A (rs12746613, P = 0.0022 replication, P = 2 x 10(-5) overall). Many of these loci are also associated to other immunologic diseases.",

keywords = "antigens, CD2, antigens, CD28, antigens, CD58, arthritis, rheumatoid, case-control studies, genetic predisposition to disease, genetic Variation, genotype, humans, polymorphism, single nucleotide, repressor proteins, risk factors",

author = "Soumya Raychaudhuri and Thomson, {Brian P} and Remmers, {Elaine F} and Stephen Eyre and Anne Hinks and Candace Guiducci and Catanese, {Joseph J} and Gang Xie and Stahl, {Eli A} and Robert Chen and Lars Alfredsson and Amos, {Christopher I} and Ardlie, {Kristin G} and Anne Barton and John Bowes and Burtt, {Noel P} and Monica Chang and Jonathan Coblyn and Costenbader, {Karen H} and Criswell, {Lindsey A} and Crusius, {J Bart A} and Jing Cui and {De Jager}, {Phillip 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 Kurreeman, {Fina A S} and Lee, {Annette T} and Xiangdong Liu and Yonghong Li and Paul Martin and Morgan, {Ann W} and Leonid Padyukov 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 Weinblatt, {Michael E} and Wilson, {Anthony G} and Wolbink, {Gert Jan} and {BIRAC consortium}",

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T1 - Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk

AU - Raychaudhuri, Soumya

AU - Thomson, Brian P

AU - Remmers, Elaine F

AU - Eyre, Stephen

AU - Hinks, Anne

AU - Guiducci, Candace

AU - Catanese, Joseph J

AU - Xie, Gang

AU - Stahl, Eli A

AU - Chen, Robert

AU - Alfredsson, Lars

AU - Amos, Christopher I

AU - Ardlie, Kristin G

AU - Barton, Anne

AU - Bowes, John

AU - Burtt, Noel P

AU - Chang, Monica

AU - Coblyn, Jonathan

AU - Costenbader, Karen H

AU - Criswell, Lindsey A

AU - Crusius, J Bart A

AU - Cui, Jing

AU - De Jager, Phillip 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 - Kurreeman, Fina A S

AU - Lee, Annette T

AU - Liu, Xiangdong

AU - Li, Yonghong

AU - Martin, Paul

AU - Morgan, Ann W

AU - Padyukov, Leonid

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 - Weinblatt, Michael E

AU - Wilson, Anthony G

AU - Wolbink, Gert Jan

AU - BIRAC consortium

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N2 - To discover new rheumatoid arthritis (RA) risk loci, we systematically examined 370 SNPs from 179 independent loci with P <0.001 in a published meta-analysis of RA genome-wide association studies (GWAS) of 3,393 cases and 12,462 controls. We used Gene Relationships Across Implicated Loci (GRAIL), a computational method that applies statistical text mining to PubMed abstracts, to score these 179 loci for functional relationships to genes in 16 established RA disease loci. We identified 22 loci with a significant degree of functional connectivity. We genotyped 22 representative SNPs in an independent set of 7,957 cases and 11,958 matched controls. Three were convincingly validated: CD2-CD58 (rs11586238, P = 1 x 10(-6) replication, P = 1 x 10(-9) overall), CD28 (rs1980422, P = 5 x 10(-6) replication, P = 1 x 10(-9) overall) and PRDM1 (rs548234, P = 1 x 10(-5) replication, P = 2 x 10(-8) overall). An additional four were replicated (P <0.0023): TAGAP (rs394581, P = 0.0002 replication, P = 4 x 10(-7) overall), PTPRC (rs10919563, P = 0.0003 replication, P = 7 x 10(-7) overall), TRAF6-RAG1 (rs540386, P = 0.0008 replication, P = 4 x 10(-6) overall) and FCGR2A (rs12746613, P = 0.0022 replication, P = 2 x 10(-5) overall). Many of these loci are also associated to other immunologic diseases.

AB - To discover new rheumatoid arthritis (RA) risk loci, we systematically examined 370 SNPs from 179 independent loci with P <0.001 in a published meta-analysis of RA genome-wide association studies (GWAS) of 3,393 cases and 12,462 controls. We used Gene Relationships Across Implicated Loci (GRAIL), a computational method that applies statistical text mining to PubMed abstracts, to score these 179 loci for functional relationships to genes in 16 established RA disease loci. We identified 22 loci with a significant degree of functional connectivity. We genotyped 22 representative SNPs in an independent set of 7,957 cases and 11,958 matched controls. Three were convincingly validated: CD2-CD58 (rs11586238, P = 1 x 10(-6) replication, P = 1 x 10(-9) overall), CD28 (rs1980422, P = 5 x 10(-6) replication, P = 1 x 10(-9) overall) and PRDM1 (rs548234, P = 1 x 10(-5) replication, P = 2 x 10(-8) overall). An additional four were replicated (P <0.0023): TAGAP (rs394581, P = 0.0002 replication, P = 4 x 10(-7) overall), PTPRC (rs10919563, P = 0.0003 replication, P = 7 x 10(-7) overall), TRAF6-RAG1 (rs540386, P = 0.0008 replication, P = 4 x 10(-6) overall) and FCGR2A (rs12746613, P = 0.0022 replication, P = 2 x 10(-5) overall). Many of these loci are also associated to other immunologic diseases.

KW - antigens, CD2

KW - antigens, CD28

KW - antigens, CD58

KW - arthritis, rheumatoid

KW - case-control studies

KW - genetic predisposition to disease

KW - genetic Variation

KW - genotype

KW - humans

KW - polymorphism, single nucleotide

KW - repressor proteins

KW - risk factors

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DO - 10.1038/ng.479

M3 - Letter

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SN - 1061-4036

VL - 41

SP - 1313

EP - 1318

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk

Abstract

Keywords

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