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

Fugmann, Cecilia ; Reid, Sarah ; Pucholt, Pascal ; Kvarnström, Marika ; Björk, Albin ; Mofors, Johannes ; Sjöwall, Christopher ; Eriksson, Per ; Olsson, Peter LU and Mandl, Thomas LU orcid , et al. (2024) In Rheumatology (Oxford, England) p.1-6
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Rheumatology (Oxford, England)
pages
1 - 6
publisher
Oxford University Press
external identifiers
  • pmid:39693120
ISSN
1462-0332
DOI
10.1093/rheumatology/keae693
language
English
LU publication?
yes
additional info
© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.
id
572543fb-ea35-4a0c-a533-84f52533c657
date added to LUP
2025-01-23 12:33:56
date last changed
2025-04-04 14:06:06
@article{572543fb-ea35-4a0c-a533-84f52533c657,
  abstract     = {{<p>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.</p><p>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).</p><p>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 &lt; 1x10-5.</p><p>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.</p>}},
  author       = {{Fugmann, Cecilia and Reid, Sarah and Pucholt, Pascal and Kvarnström, Marika and Björk, Albin and Mofors, Johannes and Sjöwall, Christopher and Eriksson, Per and Olsson, Peter and Mandl, Thomas and Forsblad-d'Elia, Helena and Magnusson Bucher, Sara and Johnsen, Svein Joar and Norheim, Katrine Brække and Appel, Silke and Hammenfors, Daniel and Jensen, Janicke Liaaen and Palm, Øyvind and Omdal, Roald and Jonsson, Roland and Baecklund, Eva and Wahren-Herlenius, Marie and Leonard, Dag and Imgenberg-Kreuz, Juliana and Nordmark, Gunnel}},
  issn         = {{1462-0332}},
  language     = {{eng}},
  month        = {{12}},
  pages        = {{1--6}},
  publisher    = {{Oxford University Press}},
  series       = {{Rheumatology (Oxford, England)}},
  title        = {{A high polygenic risk score is associated with SSA/SSB antibody positivity and early onset in primary Sjögren's disease}},
  url          = {{http://dx.doi.org/10.1093/rheumatology/keae693}},
  doi          = {{10.1093/rheumatology/keae693}},
  year         = {{2024}},
}