Bossini-Castillo, Lara ORCID: 0000-0002-5471-5824, Villanueva-Martin, Gonzalo, Kerick, Martin ORCID: 0000-0002-6298-4514, Acosta-Herrera, Marialbert, Lopez-Isac, Elena, Simeon, Carmen P., Ortego-Centeno, Norberto, Assassi, Shervin, Hunzelmann, Nicolas, Gabrielli, Armando, de Vries-Bouwstra, J. K., Allanore, Yannick, Fonseca, Carmen, Denton, Christopher P., Radstake, Timothy R. D. J., Eugenia Alarcon-Riquelme, Marta, Beretta, Lorenzo, Mayes, Maureen D. and Martin, Javier ORCID: 0000-0002-2202-0622 (2021). Genomic Risk Score impact on susceptibility to systemic sclerosis. Ann. Rheum. Dis., 80 (1). S. 118 - 128. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2060

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Abstract

Objectives Genomic Risk Scores (GRS) successfully demonstrated the ability of genetics to identify those individuals at high risk for complex traits including immune-mediated inflammatory diseases (IMIDs). We aimed to test the performance of GRS in the prediction of risk for systemic sclerosis (SSc) for the first time. Methods Allelic effects were obtained from the largest SSc Genome-Wide Association Study (GWAS) to date (9 095 SSc and 17 584 healthy controls with European ancestry). The best-fitting GRS was identified under the additive model in an independent cohort that comprised 400 patients with SSc and 571 controls. Additionally, GRS for clinical subtypes (limited cutaneous SSc and diffuse cutaneous SSc) and serological subtypes (anti-topoisomerase positive (ATA+) and anti-centromere positive (ACA+)) were generated. We combined the estimated GRS with demographic and immunological parameters in a multivariate generalised linear model. Results The best-fitting SSc GRS included 33 single nucleotide polymorphisms (SNPs) and discriminated between patients with SSc and controls (area under the receiver operating characteristic (ROC) curve (AUC)=0.673). Moreover, the GRS differentiated between SSc and other IMIDs, such as rheumatoid arthritis and Sjogren's syndrome. Finally, the combination of GRS with age and immune cell counts significantly increased the performance of the model (AUC=0.787). While the SSc GRS was not able to discriminate between ATA+ and ACA+ patients (AUC<0.5), the serological subtype GRS, which was based on the allelic effects observed for the comparison between ACA+ and ATA+ patients, reached an AUC=0.693. Conclusions GRS was successfully implemented in SSc. The model discriminated between patients with SSc and controls or other IMIDs, confirming the potential of GRS to support early and differential diagnosis for SSc.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bossini-Castillo, LaraUNSPECIFIEDorcid.org/0000-0002-5471-5824UNSPECIFIED
Villanueva-Martin, GonzaloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerick, MartinUNSPECIFIEDorcid.org/0000-0002-6298-4514UNSPECIFIED
Acosta-Herrera, MarialbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Isac, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simeon, Carmen P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortego-Centeno, NorbertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assassi, ShervinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunzelmann, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabrielli, ArmandoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Vries-Bouwstra, J. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Allanore, YannickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fonseca, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denton, Christopher P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radstake, Timothy R. D. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eugenia Alarcon-Riquelme, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beretta, LorenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayes, Maureen D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, JavierUNSPECIFIEDorcid.org/0000-0002-2202-0622UNSPECIFIED
URN: urn:nbn:de:hbz:38-604073
DOI: 10.1136/annrheumdis-2020-218558
Journal or Publication Title: Ann. Rheum. Dis.
Volume: 80
Number: 1
Page Range: S. 118 - 128
Date: 2021
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-2060
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENETIC RISK; DISEASE; PREDICTION; SURVIVAL; ASSOCIATION; PREVALENCE; CONTEXT; LOCIMultiple languages
RheumatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60407

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