A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides
Introduction. Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genet...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/113070 |
| Acceso en línea: | https://hdl.handle.net/2445/113070 |
| Access Level: | acceso abierto |
| Palabra clave: | Artritis reumatoide Genomes Genòmica Anticossos monoclonals Pèptids Rheumatoid arthritis Genomics Monoclonal antibodies Peptides |
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A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptidesBossini Castillo, LaraKovel, C. deKallberg, H.Slot, R. van 'tItaliaander, A.Coenen, M.Tak, P. P.Posthumus, M. D.Wijmenga, CiscaHuizinga, TomHelm-van Mil, A. H. M. van derStoeken-Rijsbergen, G.Rodríguez-Rodríguez, LuisBalsa, AlejandroGonzález Álvaro, IsidoroGonzález-Gay, Miguel A.Gómez Vaquero, CarmenFranke, B.LifeLines Cohort StudyVermeulen, S.Horst-Bruinsma, I. E. van derDijkmans, B. A. C.Wolbink, G. J.Ophoff, Roel A.Maehlen, M. T.Riel, P. vanMerriman, M.Klareskog, L.Lie, Benedicte A.Merriman, TonyCrusius, J. B. A.Brouwer, E.Martín, JavierVries, N. deToes, R.Padyukov, LeonidKoeleman, Bobby P. C.Artritis reumatoideGenomesGenòmicaAnticossos monoclonalsPèptidsRheumatoid arthritisGenomesGenomicsMonoclonal antibodiesPeptidesIntroduction. Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods. We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, aminoacid residues and single nucleotide polymorphisms was undertaken. Results. The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two aminoacid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions. Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition.BMJ Publishing Group2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/113070Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1136/annrheumdis-2013-204591Annals of the Rheumatic Diseases, 2015, vol. 74, num. 3, p. e15https://doi.org/10.1136/annrheumdis-2013-204591(c) BMJ Publishing Group, 2015info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1130702026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides |
| title |
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides |
| spellingShingle |
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides Bossini Castillo, Lara Artritis reumatoide Genomes Genòmica Anticossos monoclonals Pèptids Rheumatoid arthritis Genomes Genomics Monoclonal antibodies Peptides |
| title_short |
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides |
| title_full |
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides |
| title_fullStr |
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides |
| title_full_unstemmed |
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides |
| title_sort |
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides |
| dc.creator.none.fl_str_mv |
Bossini Castillo, Lara Kovel, C. de Kallberg, H. Slot, R. van 't Italiaander, A. Coenen, M. Tak, P. P. Posthumus, M. D. Wijmenga, Cisca Huizinga, Tom Helm-van Mil, A. H. M. van der Stoeken-Rijsbergen, G. Rodríguez-Rodríguez, Luis Balsa, Alejandro González Álvaro, Isidoro González-Gay, Miguel A. Gómez Vaquero, Carmen Franke, B. LifeLines Cohort Study Vermeulen, S. Horst-Bruinsma, I. E. van der Dijkmans, B. A. C. Wolbink, G. J. Ophoff, Roel A. Maehlen, M. T. Riel, P. van Merriman, M. Klareskog, L. Lie, Benedicte A. Merriman, Tony Crusius, J. B. A. Brouwer, E. Martín, Javier Vries, N. de Toes, R. Padyukov, Leonid Koeleman, Bobby P. C. |
| author |
Bossini Castillo, Lara |
| author_facet |
Bossini Castillo, Lara Kovel, C. de Kallberg, H. Slot, R. van 't Italiaander, A. Coenen, M. Tak, P. P. Posthumus, M. D. Wijmenga, Cisca Huizinga, Tom Helm-van Mil, A. H. M. van der Stoeken-Rijsbergen, G. Rodríguez-Rodríguez, Luis Balsa, Alejandro González Álvaro, Isidoro González-Gay, Miguel A. Gómez Vaquero, Carmen Franke, B. LifeLines Cohort Study Vermeulen, S. Horst-Bruinsma, I. E. van der Dijkmans, B. A. C. Wolbink, G. J. Ophoff, Roel A. Maehlen, M. T. Riel, P. van Merriman, M. Klareskog, L. Lie, Benedicte A. Merriman, Tony Crusius, J. B. A. Brouwer, E. Martín, Javier Vries, N. de Toes, R. Padyukov, Leonid Koeleman, Bobby P. C. |
| author_role |
author |
| author2 |
Kovel, C. de Kallberg, H. Slot, R. van 't Italiaander, A. Coenen, M. Tak, P. P. Posthumus, M. D. Wijmenga, Cisca Huizinga, Tom Helm-van Mil, A. H. M. van der Stoeken-Rijsbergen, G. Rodríguez-Rodríguez, Luis Balsa, Alejandro González Álvaro, Isidoro González-Gay, Miguel A. Gómez Vaquero, Carmen Franke, B. LifeLines Cohort Study Vermeulen, S. Horst-Bruinsma, I. E. van der Dijkmans, B. A. C. Wolbink, G. J. Ophoff, Roel A. Maehlen, M. T. Riel, P. van Merriman, M. Klareskog, L. Lie, Benedicte A. Merriman, Tony Crusius, J. B. A. Brouwer, E. Martín, Javier Vries, N. de Toes, R. Padyukov, Leonid Koeleman, Bobby P. C. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Artritis reumatoide Genomes Genòmica Anticossos monoclonals Pèptids Rheumatoid arthritis Genomes Genomics Monoclonal antibodies Peptides |
| topic |
Artritis reumatoide Genomes Genòmica Anticossos monoclonals Pèptids Rheumatoid arthritis Genomes Genomics Monoclonal antibodies Peptides |
| description |
Introduction. Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods. We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, aminoacid residues and single nucleotide polymorphisms was undertaken. Results. The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two aminoacid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions. Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://hdl.handle.net/2445/113070 |
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https://hdl.handle.net/2445/113070 |
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Inglés |
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Inglés |
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Reproducció del document publicat a: https://doi.org/10.1136/annrheumdis-2013-204591 Annals of the Rheumatic Diseases, 2015, vol. 74, num. 3, p. e15 https://doi.org/10.1136/annrheumdis-2013-204591 |
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(c) BMJ Publishing Group, 2015 info:eu-repo/semantics/openAccess |
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(c) BMJ Publishing Group, 2015 |
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openAccess |
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application/pdf |
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BMJ Publishing Group |
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BMJ Publishing Group |
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Articles publicats en revistes (Ciències Clíniques) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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