Objective: The study aimed to explore the causal effect of body mass index (BMI) on osteoarthritis.
Methods: The genome-wide association data of BMI and osteoarthritis were obtained via the Mendelian randomization (MR)-base platform. Single nucleotide polymorphisms (SNPs) significantly associated with BMI were identified and used as instrumental variables, and the causal relationship between BMI and osteoarthritis was examined using the two-sample MR research method. Three statistical methods including inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were employed.
Results: A total of 79 SNPs significantly associated with BMI were identified in the study (P< 5× 10^{− 8}; linkage disequilibrium r² < 0.1). Consistent association between BMI and osteoarthritis was observed when evaluated by different methods (IVW: odds ratio (OR) 1.028, 95% confidence interval (CI) 1.021– 1.036; weighted median estimator: OR 1.028, 95% CI 1.019– 1.037; MR-Egger regression: OR 1.028, 95% CI 1.009– 1.046), which suggests that BMI is positively associated with increased risk of osteoarthritis. There was no evidence that the observed causal effect between BMI and the risk of osteoarthritis was affected by genetic pleiotropy (MR-Egger intercept 1.3× 10^{− 5}, P=0.959).
Conclusion: The MR analysis provided the strong evidence to indicate that BMI might be causally associated with the risk of osteoarthritis.
Keywords: osteoarthritis, body mass index, Mendelian randomization