Knee osteoarthritis (KOA) is a common disabling joint disease that affects millions of people worldwide. Diet may play a role in the etiology and progression of KOA, but evidence for a causal relationship is limited. We aimed to investigate the causal impact of dietary intake on KOA risk using Mendelian randomization (MR). We used summary-level data from genome-wide association studies (GWAS) including dietary intake (n = 335, 394-462, 342), and KOA (n = 403, 124). We selected 6-77 genetic variants as instrumental variables for 18 dietary factors, including processed meat, poultry, beef, oily fish, non-oily fish, pork, lamb, frequency of alcohol intake, alcoholic beverages, tea, coffee, dried fruit, cereals, cheese, bread, cooked vegetables, salad/raw vegetables, and fresh fruit. We performed univariate and multivariate MR analyses to estimate the causal effect of each dietary factor on KOA risk. We also performed some sensitivity analyses to assess the validity of the MR hypothesis. We found that higher coffee intake was associated with increased KOA risk, whereas higher intake of dried fruits, grains, cheese, and oily fish was associated with reduced KOA risk. After multivariate adjustment, we found that coffee and oily fish intake may affect KOA through obesity, body mass index (BMI), diabetes, hypertension, and prolonged standing. Sensitivity analyses did not reveal any evidence of pleiotropy. Our study provides new causal evidence that dietary intake may influence KOA risk. Specifically, we suggest that increased intake of dried fruits, grains, cheese, and oily fish and decreased coffee intake may be beneficial in preventing and mitigating KOA. further studies are needed to elucidate the underlying mechanisms and to confirm our findings in different populations.
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