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Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
Open accessAbstract
The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39×10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84×10(-21), OR = 0.55) and ATA (P = 1.14×10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
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“GRB10 has been associated with a subtype of systemic sclerosis (lcSSc); patients with systemic sclerosis have higher expression of GRB10 in monocytes67,68.”
From Quantifying the contribution of Neanderthal introgression to the heritability of complex traits (2021) · cites this paper as [67]
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“GRB10 has been associated with a subtype of systemic sclerosis (lcSSc); patients with systemic sclerosis have higher expression of GRB10 in monocytes67,68.”
From Quantifying the contribution of Neanderthal introgression to the heritability of complex traits (2021) · cites this paper as [67]
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PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth457 · Cited by 14,551
Preliminary criteria for the classification of systemic sclerosis (scleroderma)
Masi, A. T. (1980) · Arthritis & Rheumatism · doi:10.1002/art.1780230510 · Cited by 4,925
Scleroderma (systemic sclerosis): classification, subsets and pathogenesis
LeRoy, E. C., Black, C. M., Fleischmajer, R., Jablonska, S., Krieg, T. M., Medsger, T. A., Rowell, N. R., & Wollheim, F. A. (2001) · CRC Press eBooks · doi:10.3109/9780203214237-95 · Cited by 3,919
A new multipoint method for genome-wide association studies by imputation of genotypes
Marchini, J., Howie, B., Myers, S., McVean, G., & Donnelly, P. (2007) · Nature Genetics · doi:10.1038/ng2088 · Cited by 2,609
Primary Pulmonary Hypertension
Rubin, L. J. (1997) · New England Journal of Medicine · doi:10.1056/nejm199701093360207 · Cited by 1,726
Hunter, D. J., Kraft, P. L., Jacobs, K. B., Cox, D. G., Yeager, M., Hankinson, S. E., Wacholder, S., Wang, Z., Welch, R. A., Hutchinson, A. A., et al. (2007) · Nature Genetics · doi:10.1038/ng2075 · Cited by 1,487
Gabrielli, A., Avvedimento, E. V., & Krieg, T. M. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0806188 · Cited by 1,420
Criteria for the classification of early systemic sclerosis.
LeRoy, E. C., & Medsger, T. A. (2001) · PubMed · Cited by 1,384
Skol, A. D., Scott, L. J., Abecasis, G. R., & Boehnke, M. (2006) · Nature Genetics · doi:10.1038/ng1706 · Cited by 1,286
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- FC Arnett, 2009, Major Histocompatibility Complex (MHC) class II alleles, haplotypes, and epitopes which confer susceptibility or protection in the fibrosing autoimmune disease systemic sclerosis: analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls., Ann Rheum Dis, 69, 822, 10.1136/ard.2009.111906 · DOI
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Items 201–229 of 229
Shu, X., Purdue, M. P., Ye, Y., Wood, C. G., Chen, M., Wang, Z., Albanes, D., Pu, X., Huang, M., Stevens, V. L., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3001 · Cited by 1
Biomarkers in Scleroderma: Current Status
Gupta, L., Phatak, S. B., & Edavalath, S. (2017) · Indian Journal of Rheumatology · doi:10.4103/0973-3698.219087 · Cited by 1
Gholizadeh, S. (2018) · eScholarship (California Digital Library) · Cited by 1
Sizemore, T. C., Merchant, G., & Whitfield, K. (2015) · International Journal of Case Reports and Images · doi:10.5348/ijcri-201587-cr-10548
Therapeutic targeting of T cells in systemic sclerosis
Cant, R., van Laar, J. M., & O’Reilly, S. (2013) · International Journal of Clinical Rheumatology · doi:10.2217/ijr.13.20
Treatment options in Raynaud's phenomenon
Hughes, M., & Herrick, A. L. (2014) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2014.883314
Self-citationGenomassoziierte Studien bei chronisch-entzündlichen Dermatosen
Rodríguez, E., & Weidinger, S. (2014) · Der Internist · doi:10.1007/s00108-013-3306-8
Transplantation rénale dans le cadre de la sclérodermie systémique : étude française multicentrique
Dehay, J. (2013) · OpenGrey (Institut de l'Information Scientifique et Technique)
FACULTE DE MEDECINE ET DE PHARMACIE DE ROUEN
François, A., Boyer, O., & Guerrot, D. (2015)
The WNT signalling pathway in systemic sclerosis
Frost, J. (2016)
Novel approaches to identify biomechanisms in systemic sclerosis
Lopez, H. (2017) · UCL Discovery (University College London)
Pathogenesis of Fibrosis—The Lung as a Model
Jefferies, C. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-47927-1.00019-0
Kotyla, P. J. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814307-0.00049-9
Pulmonary involvement in systemic sclerosis
Wells, A. U. (2019) · European Respiratory Society eBooks · doi:10.1183/2312508x.10014219
Rezaei, R., Kavosi, H., Gharibdoost, F., Mojtahedi, H., Vodjgani, M., & Mahmoudi, M. (2020) · Rheumatology Research · doi:10.22631/rr.2020.69997.1099
Using hierarchical similarity to examine the genetics of Behçet’s disease
Shenoi, S. J., & Baker, E. J. (2021) · BMC Research Notes · doi:10.1186/s13104-021-05767-6
Assassi, S., & Allanore, Y. (2016) · Springer eBooks · doi:10.1007/978-3-319-31407-5_3
Self-citationAssassi, S., & Arnett, F. C. (2014) · Springer eBooks · doi:10.1007/978-0-387-84828-0_391
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Castelino, F. V., & Dellaripa, P. F. (2014) · Springer eBooks · doi:10.1007/978-0-387-84828-0_389
Plasmacytoid Dendritic Cells in Autoimmunity
Ganguly, D. (2022) · Springer eBooks · doi:10.1007/978-981-19-5595-2_5
Ayub, S., Shah, Z. A., Shafi, T., Sofi, F. A., Bhat, I., Rasool, R., Dangroo, M. A., Baba, S. M., Ismail, N., & Majid, N. (2023) · The Egyptian Rheumatologist · doi:10.1016/j.ejr.2023.04.007
Statistical methods for gene selection and genetic association studies
Cao, X. (2023) · Digital Commons - Michigan Tech (Michigan Technological University) · doi:10.37099/mtu.dc.etdr/1575
Assassi, S., Martin, J. J., & Allanore, Y. (2024) · Springer eBooks · doi:10.1007/978-3-031-40658-4_4
Self-citationRole of regulatory T cells in pathogenesis and therapeutics of scleroderma (systemic sclerosis)
Dar, S. A., Das, S., Jawed, A., Nasreen, N., & Rai, G. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13947-5.00010-5
Skin involvement in other autoimmune diseases
Xu, Y., Tian, J., Chen, J., Hu, Q., & Zhu, H. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23947-2.00062-x
Genetic Characterization of Chicken Models for Autoimmune Disease
Sahlqvist, A. (2012) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Chen, J., Zhang, Z., Fu, Q., Hou, H., Xu, G., Li, Z., Lu, Z., Qiu, J., Wu, K., Gao, X., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1857945
Clinical application of genomic advances in systemic sclerosis
Rosa-Baez, C., Rangel‐Peláez, C., Martínez-Gutiérrez, L., Acosta‐Herrera, M., & Martín, J. (2026) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000001185
Metadata
- Authors
- Gorlova, O., Martin, J.-E., Rueda, B., Koeleman, B. P. C., Ying, J., Teruel, M., Diaz-Gallo, L.-M., Broen, J. C., Vonk, M. C., Simeon, C. P., Alizadeh, B. Z., Coenen, M. J. H., Voskuyl, A. E., Schuerwegh, A. J., van Riel, P. L. C. M., Vanthuyne, M., van 't Slot, R., Italiaander, A., Ophoff, R. A., Hunzelmann, N., Fonollosa, V., Ortego-Centeno, N., González-Gay, M. A., García-Hernández, F. J., González-Escribano, M. F., Airo, P., van Laar, J., Worthington, J., Hesselstrand, R., Smith, V., de Keyser, F., Houssiau, F., Chee, M. M., Madhok, R., Shiels, P. G., Westhovens, R., Kreuter, A., de Baere, E., Witte, T., Padyukov, L., Nordin, A., Scorza, R., Lunardi, C., Lie, B. A., Hoffmann-Vold, A.-M., Palm, Ø., García de la Peña, P., Carreira, P., Spanish Scleroderma Group, Varga, J., Hinchcliff, M., Lee, A. T., Gourh, P., Amos, C. I., Wigley, F. M., Hummers, L. K., Hummers, J., Nelson, J. L., Riemekasten, G., Herrick, A., Beretta, L., Fonseca, C., Denton, C. P., Gregersen, P. K., Agarwal, S., Assassi, S., Tan, F. K., Arnett, F. C., Radstake, T. R. D. J., Mayes, M. D., & Martin, J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- University Medical Center Utrecht (NL)
- Radboud University Nijmegen (NL)
- University Medical Center Groningen (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Leiden University (NL)
- Cliniques Universitaires Saint-Luc (BE)
- University of Cologne (DE)
- Newcastle University (GB)
- Manchester Academic Health Science Centre (GB)
- Lund University (SE)
- Ghent University (BE)
- Glasgow Royal Infirmary (GB)
- Western Infirmary (GB)
- St. Josef-Hospital (DE)
- Medizinische Hochschule Hannover (DE)
- Karolinska Institutet (SE)
- University of Milan (IT)
- University of Verona (IT)
- Oslo University Hospital (NO)
- Hospital Universitario 12 De Octubre (ES)
- Northwestern University (US)
- Feinstein Institute for Medical Research (US)
- Johns Hopkins University (US)
- Fred Hutch Cancer Center (US)
- The Royal Free Hospital (GB)
- The University of Texas Health Science Center at Houston (US)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Gorlova, Olga
- Martin, Javier
- ORCID
- Gorlova, Olga
- Koeleman, Bobby P. C.
- Broen, Jasper C.
- Alizadeh, Behrooz Z.
- Coenen, Marieke J. H.
- Voskuyl, Alexandre E.
- van Riel, Piet L. C. M.
- Ophoff, Roel A.
- van Laar, Jacob
- Worthington, Jane
- Hesselstrand, Roger
- Smith, Vanessa
- Shiels, Paul G.
- Kreuter, Alexander
- Witte, Torsten
- Padyukov, Leonid
- Lunardi, Claudio
- Lie, Benedicte A.
- Palm, Øyvind
- Carreira, Patricia
- Varga, John
- Hinchcliff, Monique
- Gourh, Pravitt
- Hummers, Laura K.
- Herrick, Ariane
- Beretta, Lorenzo
- Fonseca, Carmen
- Denton, Christopher P.
- Gregersen, Peter K.
- Agarwal, Sandeep
- Assassi, Shervin
- Radstake, Timothy R. D. J.
- Mayes, Maureen D.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-07-14
- Volume
- 7
- Issue
- 7
- Pages
- e1002178
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3136437
- OpenAlex
- W2118448966
- Cited by
- 231
- References
- 51
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 9 · 2023: 12 · 2022: 10 · 2021: 16 · 2020: 16 · 2019: 16 · 2018: 16 · 2017: 17 · 2016: 21 · 2015: 26 · 2014: 24 · 2013: 18 · 2012: 18
- FWCI
- 14.85
- Type
- journal article
- Language
- en
- Update notices
- Open access
- gold
- doi.org
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- PubMed Central (publishedVersion, cc-by)
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- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- U.S. Department of Defense (W81XWH)
- Deutsche Forschungsgemeinschaft
- ZonMw
- Diabetes Fonds (2008.40.001)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (11110)
- ReumaNederland
- European League Against Rheumatism
- Exzellenzclusters Entzündungsforschung
- Versus Arthritis (/17552)
- Sociedad Española de Reumatología
- Dutch Arthritis Association
- National Institutes of Health (5p50ar054144-05, W81XWH, n01ar002251-000)
- Instituto de Salud Carlos III
- National Institute of Mental Health (R01MH078075)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR055258, 1-P50-AR-054144, P50-AR-054144, R01AR055258, N01 AR002251, N01 AR 02251)
- Congressionally Directed Medical Research Programs (W81XWH‐07‐01‐0111)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- systemic sclerosis, genetic susceptibility, limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, anti-centromere antibodies, anti-Scl-70 antibodies, IRF8, Grb10, SOX5, HLA-DQB1, HLA-DPA1, HLA-DPB1, Notch4, genetic markers, autoantibodies, clinical phenotype
- MeSH terms
- Alleles, Autoantibodies, Female, Genetic Markers, HLA Antigens, Humans, Male, Middle Aged, Phenotype, Scleroderma, Systemic, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci
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