Association of Clonal Hematopoiesis With Incident, Late‐Onset, Seropositive Rheumatoid Arthritis
Main finding · Incident SPRAResult — go to the resultPooled hazard ratio 1.26 CI 1.03–1.52Authors' conclusion
Age-related CH, including DNMT3A-CHIP, autosomal mCA, and mLOY, are risk factors for incident SPRA but not SNRA, supporting a genotype- and serostatus-specific link between somatic mutation and RA, with the classical complement pathway as a potential modifier.
Study context
- Population
- Participants of NIH All of Us, Vanderbilt BioVU and UK Biobank3 biobanks
- Participants
- 612,989 participants
- Exposure
- Clonal hematopoiesis vs no clonal hematopoiesis
- CH of indeterminate potential (CHIP)n = 30,840
- Outcome
- Incident seropositive rheumatoid arthritis (RA) (SPRA) and seronegative RA (SNRA)
Methodological detailsmulti-biobank (NIH All of Us, Vanderbilt BioVU, UK Biobank), harmonized high-specificity phenotyping algorithm, age-scale survival models, interaction models with genetically predicted complement protein levels
- Multi-biobank (NIH All of Us, Vanderbilt BioVU, UK Biobank)
- Harmonized high-specificity phenotyping algorithm
- Age-scale survival models
- Interaction models with genetically predicted complement protein levels
Main finding
Incident SPRA
Pooled hazard ratio
1.26
CI 1.03–1.52
P = 2.3 × 10-2
CHIPvs No CH
pooled HR 1.26 (CI 1.03–1.52); P = 2.3 × 10-2
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | HR (CI) | P value | |
|---|---|---|---|
| Incident SPRA, DNMT3A-mutated CHIP and late-onset RACHIPvs No CHDNMT3A-mutated CHIP, late-onset RA | 1.45 (1.13–1.96) | P = 3.6 × 10-3 | |
| Incident SPRA, mCA (UK Biobank)Autosomal mCAvs No CH | 2.12 (1.18–3.8) | P = 1.2 × 10-2 | |
| Incident SPRA, mCA (UK Biobank)mLOYvs No CH | 2.85 (1.57–5.19) | 6.1 × 10-4 | |
| 0.20.5125Hazard ratio (log scale) |
Incident SPRA, mosaic chromosomal alteration (mCA) (UK Biobank)
- Not associated with incident SNRA
Effect modification by complement
- Higher genetically predicted levels of C1r and C1s attenuated the CHIP-SPRA association
Original publication
Association of Clonal Hematopoiesis With Incident, Late‐Onset, Seropositive Rheumatoid Arthritis. Arthritis Rheumatol. Published 16 April 2026. doi:10.
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