Sjögren's disease & overlap diseases
A high polygenic risk score is associated with SSA/SSB antibody positivity and early onset in primary Sjögren’s disease
Authors' 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.
Study context
- Population
- Patients with primary Sjögren's disease (SjD) and controls; Polygenic risk score (PRS) from single nucleotide variants (SNVs) previously associated with SjD with genome-wide significance (with HLA, 21 SNVs; without HLA, 18 SNVs)1,065 SjD, 7742 controls
- Comparison
- High PRS quartile vs low PRS
- Outcome
- Genetic risk for SjD stratified by antibodies, sex and age at diagnosis
Methodological detailspolygenic risk score, genotyped with Illumina OmniExpressExome chip
- Polygenic risk score
- Genotyped with Illumina OmniExpressExome chip
Main finding
As reported in the abstract
SSA antibody-positive SjD
Each group vs low PRS (Q1-3)Estimate (95% CI)P value
High PRS (Q4)
OR 9.16(7.75–10.85)
P = 3.7 × 10-146High PRS (Q4)
OR (SSA/SSB antibody-positive SjD) 13.67(10.88–17.32)
P = 4.6 × 10-108- High PRS classified SSA/SSB antibody-positive SjD (AUC)
- 0.86
Observational data: associations, not effects.
Further findings
SSA/SSB antibody-positive SjD, PRS without HLA (18 SNVs)
| OR (95% CI) | P value | ||
|---|---|---|---|
| PRS without HLAWeaker association than PRS with HLA | 2.09 (1.71–2.55) | P = 6.4 × 10-13 | |
| 0.20.5125Odds ratio (log scale) |
Age at diagnosis · significantly younger at diagnosis
P = 2.2 × 10-6
- Frequencies of ANA, SSA and SSA/SSB antibodies · higher frequencies in high PRS quartile
- P < 1 × 10-5
Classification of SSA/SSB antibody-positive SjD by high PRS
- AUC (very good accuracy)
- 0.86
PRS in antibody-negative SjD
- Antibody negative SjD displayed a PRS similar to controls
Original publication
A high polygenic risk score is associated with SSA/SSB antibody positivity and early onset in primary Sjögren’s disease. Rheumatology (Oxford). Published 18 December 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →