Bidirectional causal relationship between obesity and osteoarthritis: Insights from a two-sample Mendelian
Anne Kamps1, Jos Runhaar1, Katerina Trajanoska2,3
1Department of General Practice, Erasmus MC University Medical Center Rotterdam, the Netherlands.
Osteoarthritis and Cartilage Open
|July 4, 2025
Summary
Obesity, measured by body mass index (BMI), causally increases the risk of osteoarthritis (OA) in the knee, hip, and hand. The study found no evidence that OA causes obesity.
Area of Science:
- Genetics
- Epidemiology
- Orthopedics
Background:
- Osteoarthritis (OA) is a leading cause of disability globally.
- Obesity is a significant, modifiable risk factor for OA development.
Purpose of the Study:
- To investigate the causal relationship between obesity and OA.
- To determine if obesity influences OA risk or vice versa.
Main Methods:
- Utilized a two-sample Mendelian randomization (MR) approach.
- Employed body mass index (BMI) as a proxy for obesity.
- Analyzed large-scale genome-wide association study (GWAS) data from hundreds of thousands of individuals.
Main Results:
- Genetically predicted higher BMI causally increased the risk of knee, hip, and hand OA.
- Observed a stronger causal effect of BMI on weight-bearing joints (knee and hip) compared to the hand.
- Found no evidence for a causal effect of OA on BMI.
Conclusions:
- Provides strong evidence for a causal link between obesity and OA.
- Highlights obesity as a significant risk factor for OA, particularly in the knee and hip.
- Suggests further research into genetic variants underlying OA and obesity mechanisms.
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