Evidence map›Paper›PMID 39693120›Full record

ArticleRheumatology (Oxford, England)2025

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

Cecilia Fugmann, Sarah Reid, Pascal Pucholt, Marika Kvarnström, Albin Björk, Johannes Mofors, Christopher Sjöwall, Per Eriksson, Peter Olsson, Thomas Mandl and 15 more

Abstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Cecilia FugmannRheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala.ORCID 0009-0005-6078-8826
Sarah ReidRheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala.
Pascal PucholtRheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala.ORCID 0000-0003-3342-1373
Marika KvarnströmDivision of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Albin BjörkDivision of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Johannes MoforsDivision of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-1873-7169
Christopher SjöwallDepartment of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden.ORCID 0000-0003-0900-2048
Per ErikssonDepartment of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden.
Peter OlssonDepartment of Rheumatology, Skåne University Hospital, Lund University, Malmö, Sweden.
Thomas MandlDepartment of Rheumatology, Skåne University Hospital, Lund University, Malmö, Sweden.ORCID 0000-0002-7143-7088
Helena Forsblad-d'EliaDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0001-7871-5303
Sara Magnusson BucherRheumatology, Örebro University, Örebro, Sweden.
Svein Joar JohnsenDepartment of Rheumatology, Stavanger University Hospital, Stavanger, Norway.ORCID 0000-0002-1591-9250
Katrine Brække NorheimDepartment of Rheumatology, Stavanger University Hospital, Stavanger, Norway.
Silke AppelBroegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID 0000-0002-2199-2315
Daniel HammenforsDepartment of Rheumatology, Haukeland University Hospital, Bergen, Norway.
Janicke Liaaen JensenDepartment of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway.ORCID 0000-0003-4276-9611
Øyvind PalmDepartment of Rheumatology, Oslo University Hospital, Oslo, Norway.
Roald OmdalResearch Department, Stavanger University Hospital, Stavanger, Norway.
Roland JonssonBroegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID 0000-0002-9588-0260
Eva BaecklundRheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala.ORCID 0000-0001-5033-0188
Marie Wahren-HerleniusDivision of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-0915-7245
Dag LeonardRheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala.ORCID 0000-0002-6275-7282
Juliana Imgenberg-KreuzRheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala.ORCID 0000-0002-7230-8990
Gunnel NordmarkRheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Sweden, Uppsala.ORCID 0000-0002-3829-7431

Funding

Agnes and Mac Rudberg foundationBrunnberg foundation, Uppsala UniversityK&A Wallenberg FoundationK&A Wallenberg Foundation KAW 2014.0272King Gustaf V's 80-year FoundationKnut and Alice Wallenberg FoundationNational Genomics InfrastructureNorwegian Research CouncilScience for Life Laboratory. ResourcesSNP&SEQ Technology Platform in UppsalaStockholm County CouncilSwedish National Infrastructure for ComputingSwedish Research CouncilSwedish Research Council 2018-05973Swedish Research Council VR#2021-02503Swedish Research Council VR #2022-00637Swedish Rheumatism AssociationThe Swedish Heart-Lung FoundationUppsala Multidisciplinary Center for Advanced Computational ScienceWellcome TrustWellcome Trust WT064890Wellcome Trust WT090532Wellcome Trust WT098017
6 · The paper itself

Abstract

objectivesTo 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.

methodsPatients 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).

resultsA 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.

conclusionA 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.

Indexed as

Antibodies, AntinuclearMultifactorial InheritanceSjogren's SyndromeAdultAgedAge of OnsetFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideRisk FactorsAntibodies, AntinuclearSS-A antibodiesantinuclear antibodiesgenome-wide association studies (GWAS)HLApolygenic risk score (PRS)single nucleotide variant (SNV)Sjögren’s diseaseSSASSB

Identifiers

PMID39693120
PMCPMC12212914

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.