A sex- and site-specific relationship between body mass index and osteoarthritis: evidence from observational and genetic analyses
Authors' conclusion
Our work demonstrates an intrinsic relationship underlying BMI and overall OA, reflected by a pronounced phenotypic association, significant biological pleiotropy, and a putative causal link.
Study context
- Population
- UK Biobank participants; largest GWAS of body mass index (BMI) and overall osteoarthritis (OA)
- Exposure
- Per 5 kg/m² increment in BMI
- Outcome
- Phenotypic and genetic links between BMI and overall OA
Methodological detailsgenetic correlation, cross-trait meta-analysis, TWAS, Mendelian randomization, UK Biobank, GWAS summary statistics, sex- and site-specific stratified analyses
- Genetic correlation, cross-trait meta-analysis, TWAS, Mendelian randomization
- UK Biobank
- GWAS summary statistics
- Sex- and site-specific stratified analyses
Main finding
As reported in the abstract
Diagnosed OA per 5 kg/m² increment in BMI (observational)
- HR for diagnosed OA per 5 kg/m² BMI increment
- 1.38 (95% CI 1.37-1.39)
- Overall genetic correlation BMI–OA (rg); P = 4.72 × 10-133
- 0.43
- Significant local genetic correlation signals
- 11
- Pleiotropic loci shared between BMI and OA (cross-trait meta-analysis)
- 34
- Novel pleiotropic loci
- seven
- Shared gene-tissue pairs (TWAS), targeting nervous, digestive and exo/endocrine systems
- 29
- Mendelian randomization OR for BMI-OA causal relationship
- 1.47 (95% CI 1.42-1.52)
Observational data: associations, not effects.
Further findings
Sex- and site-specific analyses
- Similar pattern of effects; BMI affected OA comparably in both sexes and most strongly in the knee
Original publication
A sex- and site-specific relationship between body mass index and osteoarthritis: evidence from observational and genetic analyses. Osteoarthritis Cartilage. Published 6 March 2023. doi:10.
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