2022
DOI: 10.3390/nu14183683
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Genetic Causal Association between Iron Status and Osteoarthritis: A Two-Sample Mendelian Randomization

Abstract: 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 associa… Show more

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Cited by 86 publications
(45 citation statements)
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“…Using rs800562, rs1799945, rs855791, and rs8177240 as the instruments of nutritional iron and summary data from the UK Biobank and arcOGEN cohorts, no significant association was observed between the iron and knee OA, hip OA, or overall OA, but the positive causal effect of iron levels on overall OA was observed in females ( Qu et al, 2020 ). Using the instruments from the Genetics of Iron Status Consortium and the summary-level data of outcomes from the UK Biobank and arcOGEN cohorts, Xu et al (2022) found that transferrin saturation was positively associated with both knee OA and hip OA, transferrin was negatively associated with hip OA, but serum iron and ferritin did not show a prominent effect on OA outcomes. In our study, we assessed the iron status using four biomarkers with three instrument sets while the previous studies used one biomarker with three or four instruments.…”
Section: Discussionmentioning
confidence: 99%
“…Using rs800562, rs1799945, rs855791, and rs8177240 as the instruments of nutritional iron and summary data from the UK Biobank and arcOGEN cohorts, no significant association was observed between the iron and knee OA, hip OA, or overall OA, but the positive causal effect of iron levels on overall OA was observed in females ( Qu et al, 2020 ). Using the instruments from the Genetics of Iron Status Consortium and the summary-level data of outcomes from the UK Biobank and arcOGEN cohorts, Xu et al (2022) found that transferrin saturation was positively associated with both knee OA and hip OA, transferrin was negatively associated with hip OA, but serum iron and ferritin did not show a prominent effect on OA outcomes. In our study, we assessed the iron status using four biomarkers with three instrument sets while the previous studies used one biomarker with three or four instruments.…”
Section: Discussionmentioning
confidence: 99%
“…Therefore, we chose SNPs as IVs associated at this significance level since there were not enough SNPs associated at the genome-wide significant threshold of 5 × 10 −8 [ 27 , 28 ]. Secondly, we used the PhenoScanner tool to ensure whether the IVs were significantly correlated with the risk factors for GDM [ 29 , 30 ]. In addition, we used the ’’clump_data’’ function on MR-Base to select independent SNPs (linkage disequilibrium (LD) R 2 = 0.001, >10,000 kb) [ 31 ].…”
Section: Methodsmentioning
confidence: 99%
“…158 A weighted median analysis based on large-scale genome-wide association studies (GWASs) showed that serum iron, ferritin, and transferrin saturation was positively correlated with knee osteoarthritis. 159 These observational clinical investigations have all shown an association between iron status and osteoarthritis. Animal experiments have also revealed that iron overload accelerates osteoarthritis progression.…”
Section: Ferroptosis Triggers Osteoarthritismentioning
confidence: 99%