Uncovering causal genetic mediators linking redefined obesity to osteoarthritis: Multidimensional analysis from population to genetic mechanisms
Main finding · OAResult — go to the resultOdds ratio 1.421 95 % CI 1.048–1.925Authors' conclusion
Obesity exerts a causal effect on OA, partially mediated by the downregulation of MAPK3 and RBM6.
Study context
- Population
- US National Health and Nutrition Examination Survey (NHANES) participants, 2011–2018NHANES 2011–2018
- Participants
- 8,981 participants
- Exposure
- Obesity vs no obesity
- Outcome
- OA
Methodological detailsNHANES 2011-2018, logistic regression and subgroup analyses, LDSC genetic correlation, two-sample Mendelian randomization, transcriptome-wide association studies (TWAS) and colocalization, mediation Mendelian randomization (MR)
- NHANES 2011-2018
- Logistic regression and subgroup analyses
- LDSC genetic correlation
- Two-sample Mendelian randomization
- TWAS and colocalization
- Mediation MR
Main finding
As reported in the abstract
Odds ratio
1.421
95 % CI 1.048–1.925
P = 0.025
Obesityvs No obesity
OR 1.421 (95 % CI 1.048–1.925); P = 0.025
Observational data: associations, not effects.
Further findings
| Outcome | IVW OR (95 % CI) | P value | |
|---|---|---|---|
| Causal effect of obesity on OA (MR, IVW)No reverse causality detected | 2.349 (2.012–2.743) | P < 0.001 | |
| 0.20.5125IVW OR (log scale) |
Mediation of obesity-OA pathway by genes (mediation MR)
- MAPK3 mediating effect, β
- 0.991
- MAPK3 P
- P = 0.015
- RBM6 mediating effect, β
- 2.740
- RBM6 P
- P < 0.001
- TWAS and colocalization identified MAPK3, RBM6, and PRMT6 as potential mediators
Original publication
Uncovering causal genetic mediators linking redefined obesity to osteoarthritis: Multidimensional analysis from population to genetic mechanisms. Osteoarthritis Cartilage. Published 9 November 2025. doi:10.
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