Rheumatology (Oxford, England) · 2025
A high polygenic risk score is associated with SSA/SSB antibody positivity and early onset in primary Sjögren's disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Fugmann Cecilia, Reid Sarah, Pucholt Pascal, Kvarnström Marika, Björk Albin, Mofors Johannes, Sjöwall Christopher, Eriksson Per, Olsson Peter, Mandl Thomas, Forsblad-d'Elia Helena, Magnusson Bucher Sara, Johnsen Svein Joar, Norheim Katrine Brække, Appel Silke, Hammenfors Daniel, Jensen Janicke Liaaen, Palm Øyvind, Omdal Roald, Jonsson Roland, Baecklund Eva, Wahren-Herlenius Marie, Leonard Dag, Imgenberg-Kreuz Juliana, Nordmark Gunnel
Аннотация
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 = 3.7 × 10-146), and strengthened in SjD positive for both SSA/SSB antibodies (OR 13.67, 95% CI 10.88-17.32, P = 4.6 × 10-108). 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 = 6.4 × 10-13). 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 = 2.2 × 10-6, and presented higher frequencies of ANA, SSA and SSA/SSB antibodies, P < 1 × 10-5.
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.
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 = 3.7 × 10-146), and strengthened in SjD positive for both SSA/SSB antibodies (OR 13.67, 95% CI 10.88-17.32, P = 4.6 × 10-108). 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 = 6.4 × 10-13). 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 = 2.2 × 10-6, and presented higher frequencies of ANA, SSA and SSA/SSB antibodies, P < 1 × 10-5.
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.