Lupus & antiphospholipid syndrome
Methylation and polygenic risk scores capture different features of Systemic Lupus Erythematosus
Authors' conclusion
The MRS defines an IFN-high, HLA-DRB1*03:01-linked SLE subset with multiple autoantibodies, partly distinct from PRS-associated nephritis risk, highlighting potentially divergent pathogenic pathways.
Study context
- Population
- Patients fulfilling ≥4 ACR-82 criteria for SLE and controls
- Exposure
- SLE methylation risk score (MRS) vs non-HLA polygenic risk score (PRS) and HLA-DRB1*03:01 in relation to clinical and immunological phenotypes
- Outcome
- Associations of MRS and PRS with phenotypes
Methodological detailscase-control, discovery and replication cohorts, Illumina HM450K methylation array, Immunochip genotyping
- Case-control
- Discovery and replication cohorts
- Illumina HM450K methylation array
- Immunochip genotyping
Main finding
As reported in the abstract
- Higher MRS associated with serum IFN-α2 levels
- P = 1.04 × 10-14
- Higher MRS associated with DLE, immunologic involvement and anti-SSA/SSB/RNP/Sm autoantibodies, both cohorts
- all P < 0.05
- Higher MRS associated with higher disease activity, discovery cohort
- P = 1.50 × 10-4
- MRS elevated in patients with multiple autoantibodies
- P < 1.0 × 10-15
- MRS elevated in HLA-DRB1*03:01 carriers
- P < 1.0 × 10-3
- Higher PRS associated with nephritis, anti-dsDNA positivity and lower prevalence of anti-SSB antibodies
- all P < 0.05
- No correlation between MRS and PRS
- P = 0.35
Observational data: associations, not effects.
Original publication
Methylation and polygenic risk scores capture different features of Systemic Lupus Erythematosus. Rheumatology (Oxford). Published 10 July 2026. doi:10.
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