Abstract
OBJECTIVE: We believe that there is a causal relationship between waist circumference and knee osteoarthritis. To confirm the hypothesis, we have conducted this study. METHODS: Genetic variants associated with the five anthropometric variables were obtained from previous large-scale genomewide association studies. Summary-level data on osteoarthritis were obtained from the UK Biobank. The univariable and multivariable MR framework were used to evaluate the associations. The two-sided p value was considered to be statistically significant at 0.01 (where p = 0.05/5) after Bonferroni correction for the five exposure variables. RESULTS: In the univariable MR, there was evidence of a detrimental effect of height, weight, BMI, waist circumference, and hip circumference on osteoarthritis risk in the main IVW analyses (height: OR 1.115, 95% CI 1.054-1.180; weight: OR 1.765, 95% CI 1.650-1.889; BMI: OR 1.952, 95%CI 1.841-2.068; waist circumference: OR 2.140, 95% CI 1.994-2.296; hip circumference: OR 1.719, 95% CI 1.600-1.846). And the analyses on knee osteoarthritis and hip osteoarthritis yielded similar results. However, the multivariable MR showed that only waist circumference was causally associated with osteoarthritis, after adjusting for the confounding exposure effects (waist circumference: OR 1.877, 95% CI 1.286-2.739). Such association was also repeated in the analyses on knee osteoarthritis but not hip osteoarthritis. CONCLUSION: Our study highlighted the causal associations between waist circumference and knee osteoarthritis risk.