Causal Factors for Knee, Hip, and Hand Osteoarthritis: A Mendelian Randomization Study in the UK Biobank

Area of Science:

• Genetics and Epidemiology
• Rheumatology
• Public Health

Background:

• Osteoarthritis (OA) is a prevalent degenerative joint disease with no cure.
• Identifying causal risk factors is crucial for developing effective prevention and treatment strategies for OA.
• Previous research has suggested associations between various factors and OA, but causal links remain to be fully elucidated.

Purpose of the Study:

• To investigate the causal relationships between key risk factors and the development of knee, hip, and hand osteoarthritis (OA).
• To utilize Mendelian randomization (MR) to assess causality for body mass index (BMI), bone mineral density (BMD), and other metabolic factors in relation to OA.
• To differentiate the causal impact of these factors on OA at different joint sites (weight-bearing vs. non-weight-bearing).

Main Methods:

• Analysis of individual-level data from 384,838 UK Biobank participants.
• Mendelian randomization (MR) analyses were employed to test causality for genetically predicted BMI, BMD, lipid levels, type 2 diabetes, systolic blood pressure (BP), and C-reactive protein (CRP).
• Osteoarthritis was defined by hospital diagnoses, with specific counts for all sites, knee, hip, and hand OA.

Main Results:

• Genetically determined body mass index (BMI) showed a robust causal association with all OA, knee OA, and hip OA, but not hand OA.
• Increased genetically determined femoral neck bone mineral density (BMD) was causally linked to all OA, knee OA, and hip OA.
• Low systolic blood pressure (BP) was causally associated with all OA, knee OA, and hip OA, while other tested metabolic factors and CRP levels showed no evidence of causality.

Conclusions:

• Body mass index (BMI) significantly contributes causally to the risk of osteoarthritis in weight-bearing joints (knee and hip), but not in the hand.
• High femoral neck bone mineral density (BMD) and low systolic blood pressure (BP) are identified as causal factors for generalized, knee, and hip OA.
• The study found no evidence of causality for other investigated metabolic factors or C-reactive protein (CRP) in relation to OA development.