Does smoking protect against developing osteoarthritis? Evidence from a genetically informed perspective.

Area of Science:

• Genetics and Epidemiology
• Musculoskeletal Health
• Public Health

Background:

• Observational studies suggest an inverse relationship between smoking and osteoarthritis (OA), but confounding factors like obesity may influence these findings.
• Investigating the causal link between smoking and OA is crucial for public health strategies.
• Genetic epidemiology offers a robust approach to disentangle causal relationships from observational biases.

Purpose of the Study:

• To determine the independent causal effect of smoking on the risk of developing osteoarthritis.
• To differentiate the impact of smoking from that of obesity on OA development using a genetic approach.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) study design.
• Utilized summary-level data from large genome-wide association studies (GWAS) for smoking initiation, body mass index (BMI), and OA.
• Selected genetic variants associated with smoking initiation and BMI as instrumental variables.

Main Results:

• Genetically predicted smoking initiation was significantly associated with an increased risk of overall OA, hip OA, knee OA, and hip/knee OA.
• Increased BMI was also strongly associated with higher OA risk.
• Multivariable MR analysis confirmed a significant independent causal effect of smoking initiation on OA risk, even after accounting for BMI.

Conclusions:

• This study provides strong evidence for a direct causal effect of smoking on increasing osteoarthritis risk.
• Findings underscore the importance of smoking cessation interventions and obesity management in mitigating the substantial public health burden of OA.
• Public health initiatives should prioritize addressing both smoking and obesity to combat the rising prevalence of osteoarthritis.