Mosaic loss of chromosome Y characterises late-onset rheumatoid arthritis and contrasting associations of polygenic risk score based on age at onset
Authors' conclusion
LORA was characterised by the presence of a high burden of mLOY. The observed interaction between mLOY and PRS in LORA, but not in YORA, supports different gene-environment interactions between the subsets.
Study context
- Population
- Japanese rheumatoid arthritis (RA) cases and controls; Mosaic chromosomal alterations (mCAs) detected in peripheral blood samples (Set 1: 2107 RA cases and 86,998 controls; Set 2: 2359 RA cases and 86,998 controls)2 datasets
- Comparison
- RA cases vs controls, by mosaic chromosomal alterations; Late-onset RA (LORA) and young-onset RA (YORA) separately
- Controlsn = 86,998reference
- Outcome
- Association between mCAs (incl. mosaic loss of Y) and RA, LORA and YORA
Methodological details2 independent Japanese datasets, logistic regression, meta-analysis
- 2 independent Japanese datasets
- Logistic regression
- Meta-analysis
Main finding
As reported in the abstract
mLOY
Odds ratio
1.43
P = 0.0070
LORA
Odds ratio
0.66
P = 0.0034
YORA
Observational data: associations, not effects.
Further findings
Autosomal mCAs or mosaic loss of X
- Consistently negative associations with RA, LORA and YORA
Polygenic risk score (PRS) effect sizes
- Lower for LORA than for YORA
Interaction mosaic loss of Y (mLOY) (high cell fraction) × PRS
- Strengthened association between PRS and LORA
- P = 0.0036
- Association with YORA independent of mLOY
Original publication
Mosaic loss of chromosome Y characterises late-onset rheumatoid arthritis and contrasting associations of polygenic risk score based on age at onset. Ann Rheum Dis. Published 21 February 2025. doi:10.
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