Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study
BackgroundAlthough well-documented, the causal relationships between diet-derived circulating antioxidants, oxidative stress, and osteoarthritis (OA) are equivocal. The objective of this study is to employ two-sample Mendelian randomization (MR) to investigate possible causal relationships among die...
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2023.1233086/full |
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| author | Yidan Tang Yidan Tang Xiaolin Xu Xiaolin Xu Shuangyi Zhang Shuangyi Zhang Weishuang Kong Weiyi Zhang Weiyi Zhang Tao Zhu Tao Zhu |
| author_facet | Yidan Tang Yidan Tang Xiaolin Xu Xiaolin Xu Shuangyi Zhang Shuangyi Zhang Weishuang Kong Weiyi Zhang Weiyi Zhang Tao Zhu Tao Zhu |
| author_sort | Yidan Tang |
| collection | DOAJ |
| description | BackgroundAlthough well-documented, the causal relationships between diet-derived circulating antioxidants, oxidative stress, and osteoarthritis (OA) are equivocal. The objective of this study is to employ two-sample Mendelian randomization (MR) to investigate possible causal relationships among dietary-derived circulating antioxidants, oxidative stress damage indicators, and OA risk.MethodsSingle-nucleotide polymorphisms for diet-derived circulating antioxidants (ascorbate, β-carotene, lycopene, retinol, and α-and γ-tocopherol), assessed as absolute levels and metabolites, as well as oxidative stress injury biomarkers (GSH, GPX, CAT, SOD, albumin, and total bilirubin), were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene–OA associations were obtained from publicly available and two relatively large-scale GWAS meta-analyses to date. The inverse-variance weighting method was utilized as the primary MR analysis. Moreover, multivariable MR was used to determine if mediators (BMI and smoking) causally mediated any connection. Furthermore, for each exposure, MR analyses were conducted per outcome database and then meta-analyzed.ResultsGenetically predicted absolute retinol level was causally associated with hip OA risk [odds ratios (ORs) = 0.40, 95% confidence interval (CI) = 0.24–0.68, FDR-corrected p = 0.042]. Moreover, genetically predicted albumin level was causally associated with total OA risk (OR = 0.80, 95% CI = 0.75–0.86, FDR-corrected p = 2.20E-11), as well as the risk of hip OA (OR = 0.75, 95% CI = 0.68–0.84, FDR-corrected p = 1.38E-06) and knee OA (OR = 0.82, 95% CI = 0.76–0.89, FDR-corrected p = 4.49E-06). In addition, MVMR confirmed that the effect of albumin on hip OA is independent of smoking initiation, alcoholic drinks per week, and moderate-to-vigorous physical activity levels but may be influenced by BMI.ConclusionEvidence from our study supports a potentially protective effect of high levels of retinol and albumin on OA risk. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-08T00:21:05Z |
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| spelling | doaj.art-8bbde2956fc246e0a709e1bc09e9a5712024-02-16T10:12:52ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2023-12-011010.3389/fnut.2023.12330861233086Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization studyYidan Tang0Yidan Tang1Xiaolin Xu2Xiaolin Xu3Shuangyi Zhang4Shuangyi Zhang5Weishuang Kong6Weiyi Zhang7Weiyi Zhang8Tao Zhu9Tao Zhu10Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Surgery, Xuanwei Hospital of Traditional Chinese Medicine, Xuanwei, ChinaDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaBackgroundAlthough well-documented, the causal relationships between diet-derived circulating antioxidants, oxidative stress, and osteoarthritis (OA) are equivocal. The objective of this study is to employ two-sample Mendelian randomization (MR) to investigate possible causal relationships among dietary-derived circulating antioxidants, oxidative stress damage indicators, and OA risk.MethodsSingle-nucleotide polymorphisms for diet-derived circulating antioxidants (ascorbate, β-carotene, lycopene, retinol, and α-and γ-tocopherol), assessed as absolute levels and metabolites, as well as oxidative stress injury biomarkers (GSH, GPX, CAT, SOD, albumin, and total bilirubin), were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene–OA associations were obtained from publicly available and two relatively large-scale GWAS meta-analyses to date. The inverse-variance weighting method was utilized as the primary MR analysis. Moreover, multivariable MR was used to determine if mediators (BMI and smoking) causally mediated any connection. Furthermore, for each exposure, MR analyses were conducted per outcome database and then meta-analyzed.ResultsGenetically predicted absolute retinol level was causally associated with hip OA risk [odds ratios (ORs) = 0.40, 95% confidence interval (CI) = 0.24–0.68, FDR-corrected p = 0.042]. Moreover, genetically predicted albumin level was causally associated with total OA risk (OR = 0.80, 95% CI = 0.75–0.86, FDR-corrected p = 2.20E-11), as well as the risk of hip OA (OR = 0.75, 95% CI = 0.68–0.84, FDR-corrected p = 1.38E-06) and knee OA (OR = 0.82, 95% CI = 0.76–0.89, FDR-corrected p = 4.49E-06). In addition, MVMR confirmed that the effect of albumin on hip OA is independent of smoking initiation, alcoholic drinks per week, and moderate-to-vigorous physical activity levels but may be influenced by BMI.ConclusionEvidence from our study supports a potentially protective effect of high levels of retinol and albumin on OA risk.https://www.frontiersin.org/articles/10.3389/fnut.2023.1233086/fullantioxidantoxidative stressosteoarthritiscausal effectMendelian |
| spellingShingle | Yidan Tang Yidan Tang Xiaolin Xu Xiaolin Xu Shuangyi Zhang Shuangyi Zhang Weishuang Kong Weiyi Zhang Weiyi Zhang Tao Zhu Tao Zhu Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study Frontiers in Nutrition antioxidant oxidative stress osteoarthritis causal effect Mendelian |
| title | Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study |
| title_full | Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study |
| title_fullStr | Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study |
| title_full_unstemmed | Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study |
| title_short | Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study |
| title_sort | genetic liability for diet derived circulating antioxidants oxidative stress and risk of osteoarthritis a mendelian randomization study |
| topic | antioxidant oxidative stress osteoarthritis causal effect Mendelian |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2023.1233086/full |
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