{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:00:15Z","timestamp":1753891215541,"version":"3.41.2"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the causal associations of diet-derived circulating antioxidants with knee osteoarthritis (OA), hip OA, and rheumatoid arthritis (RA) within the two-sample Mendelian randomization (MR) framework.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Independent single-nucleotide polymorphisms (SNPs) significantly associated with circulating levels of diet-derived antioxidants (retinol, \u03b2-carotene, lycopene, vitamin C and vitamin E) were extracted as genetic instruments. Summary statistics of genetic instruments associated with knee OA, hip OA, and RA were obtained from corresponding genome-wide association studies (GWASs). The inverse-variance weighted (IVW) was applied as the primary analysis method, with four sensitivity analysis approaches employed to evaluate the robustness of the primary results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically determined per unit increment of absolute circulating levels of retinol was significantly associated with a reduced risk of hip OA [odds ratio (OR)\u2009=\u20090.45, 95% confidence interval (CI) 0.26\u20130.78, <jats:italic>p<\/jats:italic>\u2009=\u20094.43\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>], while genetically determined per unit increase in absolute circulating levels of \u03b2-carotene was suggestively associated with increased risk of RA (OR\u2009=\u20091.32, 95% CI 1.07\u20131.62, <jats:italic>p<\/jats:italic>\u2009=\u20099.10\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>). No other causal association was found. Significant evidence for heterogeneity and pleiotropic outlier was only identified when absolute circulating vitamin C was evaluated as the exposure, whereas all sensitive analysis provided consistently non-significant results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrated that genetically determined lifelong higher exposure to absolute circulating levels of retinol is associated with a decreased risk of hip OA. Further MR study with more genetic instruments for absolute circulating levels of antioxidants are needed to confirm our results.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1147365","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T09:56:33Z","timestamp":1687341393000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Diet-derived circulating antioxidants and risk of knee osteoarthritis, hip osteoarthritis and rheumatoid arthritis: a two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"10","author":[{"given":"Li","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengqiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenming","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifeng","family":"Mai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianmeng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Cen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, 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