A high polygenic risk score is associated with SSA/SSB antibody positivity and early onset in primary Sjögren's disease.

Autor:	Fugmann C; Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala., Reid S; Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala., Pucholt P; Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala., Kvarnström M; Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.; Center for Rheumatology, Academic Specialist Center, Stockholm, Sweden., Björk A; Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.; Center for Rheumatology, Academic Specialist Center, Stockholm, Sweden., Mofors J; Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden., Sjöwall C; Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden., Eriksson P; Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden., Olsson P; Department of Rheumatology, Skåne University Hospital, Lund University, Malmö, Sweden., Mandl T; Department of Rheumatology, Skåne University Hospital, Lund University, Malmö, Sweden., Forsblad-d'Elia H; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Magnusson Bucher S; Rheumatology, Örebro University, Sweden, Örebro., Johnsen SJ; Department of Rheumatology, Stavanger University Hospital, Stavanger, Norway., Norheim KB; Department of Rheumatology, Stavanger University Hospital, Stavanger, Norway., Appel S; Research Department, Stavanger University Hospital, Stavanger, Norway., Hammenfors D; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway., Jensen JL; Department of Rheumatology, Haukeland University Hospital, Bergen, Norway., Palm Ø; Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway., Omdal R; Research Department, Stavanger University Hospital, Stavanger, Norway.; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway., Jonsson R; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway., Baecklund E; Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala., Wahren-Herlenius M; Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway., Leonard D; Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala., Imgenberg-Kreuz J; Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala., Nordmark G; Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Dec 18. Date of Electronic Publication: 2024 Dec 18.
DOI:	10.1093/rheumatology/keae693
Abstrakt:	Objectives: To calculate a polygenic risk score (PRS) based on single nucleotide variants (SNVs) previously associated with primary Sjögren's disease (SjD) with genome-wide significance, and determine the genetic risk for SjD stratified by antibodies, sex and age at diagnosis. Methods: Patients with SjD (n = 1065) were genotyped using Illumina OmniExpressExome chip. Control genotype data were available (n = 7742). Two PRSs were constructed, one including HLA gene variants (n = 21 SNVs), and one without HLA (n = 18 SNVs). High PRS quartile (Q4) individuals were compared with low PRS (Q1-3). Results: A high PRS was associated with SSA antibody positive SjD (OR 9.16, 95% CI 7.75-10.85, p= 3.7x10-146), and strengthened in SjD positive for both SSA/SSB antibodies (OR 13.67, 95% CI 10.88-17.32, p= 4.6x10-108). High PRS classified SSA/SSB antibody positive SjD with very good accuracy (AUC 0.86). PRS without HLA showed a weaker association with SSA/SSB positive SjD (OR 2.09, 95% CI 1.71-2.55, p= 6.4x10-13). Antibody negative SjD displayed a PRS similar to controls. Patients in the high PRS quartile were significantly younger at diagnosis, 48.9 ± 14.9 vs 53.4 ± 13.4 years in the low PRS quartiles (Q1-3), p= 2.2x10-6, and presented higher frequencies of ANA, SSA and SSA/SSB antibodies, p < 1x10-5. Conclusion: A high PRS is associated with SSA/SSB antibody positivity and early disease onset, both largely attributed to the weight of the HLA alleles. Integration of PRS with other biomarkers applied to clinical phenotypes, could be a useful tool for disease risk stratification and treatment decisions. (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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