{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:46:41Z","timestamp":1791600401398,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974347"],"award-info":[{"award-number":["81974347"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802210"],"award-info":[{"award-number":["81802210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFS0122"],"award-info":[{"award-number":["2021YFS0122"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Science and Technology of Sichuan Province","award":["81974347"],"award-info":[{"award-number":["81974347"]}]},{"name":"Department of Science and Technology of Sichuan Province","award":["81802210"],"award-info":[{"award-number":["81802210"]}]},{"name":"Department of Science and Technology of Sichuan Province","award":["2021YFS0122"],"award-info":[{"award-number":["2021YFS0122"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objective: Observational studies have shown the association between iron status and osteoarthritis (OA). However, due to difficulties of determining sequential temporality, their causal association is still elusive. Based on the summary data of genome-wide association studies (GWASs) of a large-scale population, this study explored the genetic causal association between iron status and OA. Methods: First, we took a series of quality control steps to select eligible instrumental SNPs which were strongly associated with exposure. The genetic causal association between iron status and OA was analyzed using the two-sample Mendelian randomization (MR). Inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were used for analysis. The results were mainly based on IVW (random effects), followed by sensitivity analysis. IVW and MR-Egger were used for heterogeneity testing. MR-Egger was also used for pleiotropy testing. Leave-one-SNP-out analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Maximum likelihood, penalized weighted median, and IVW (fixed effects) were performed to further validate the reliability of results. Results: IVW results showed that transferrin saturation had a positive causal association with knee osteoarthritis (KOA), hip osteoarthritis (HOA) and KOA or HOA (p &lt; 0.05, OR &gt; 1), and there was a negative causal association between transferrin and HOA and KOA or HOA (p &lt; 0.05, OR &lt; 1). The results of heterogeneity test showed that our IVW analysis results were basically free of heterogeneity (p &gt; 0.05). The results of the pleiotropy test showed that there was no pleiotropy in our IVW analysis (p &gt; 0.05). The analysis results of maximum likelihood, penalized weighted median and IVW (fixed effects) were consistent with our IVW results. No genetic causal association was found between serum iron and ferritin and OA. Conclusions: This study provides evidence of the causal association between iron status and OA, which provides novel insights to the genetic research of OA.<\/jats:p>","DOI":"10.3390\/nu14183683","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T01:51:57Z","timestamp":1662515517000},"page":"3683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":155,"title":["Genetic Causal Association between Iron Status and Osteoarthritis: A Two-Sample Mendelian Randomization"],"prefix":"10.3390","volume":"14","author":[{"given":"Jiawen","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"},{"name":"Department of Orthopedics, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[{"name":"Healthy Food Evaluation Research Center, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuangang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaibo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Orthopedic Research Institute, Sichuan University West China Hospital, 37# Guoxue Road, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/S0140-6736(20)32230-3","article-title":"Osteoarthritis in 2020 and beyond: A Lancet Commission","volume":"396","author":"Hunter","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.joca.2018.11.001","article-title":"Osteoarthritis year in review 2018: Clinical","volume":"27","author":"Mandl","year":"2019","journal-title":"Osteoarthr. 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