Department of Orthopaedics, Honghui Hospital, Xi'an Jiao Tong University, Xi'an, 710000, China.
Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
Sci Rep. 2024 May 2;14(1):10099. doi: 10.1038/s41598-024-60676-5.
The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization (MR) analysis to explore the causal relationship between circulating alpha-tocopherol levels (main forms of vitamin E in our body) and OA. The instrumental variables (IVs) of circulating alpha-tocopherol levels were obtained from a Genome-wide association study (GWAS) dataset of 7781 individuals of European descent. The outcome of OA was derived from the UK biobank. Two-sample MR analysis was used to estimate the causal relationship between circulating alpha-tocopherol levels and OA. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic in this work. The heterogeneity effect of instrumental IVs was detected by MR-Egger and IVW analyses. Sensitivity analysis was performed by removing single nucleotide polymorphism (SNP) one by one. Three SNPs (rs964184, rs2108622, and rs11057830) (P < 5E-8) strongly associated with circulating alpha-tocopherol levels were used in this analysis. The IVW-random effect indicated no causal relationship between circulating alpha-tocopherol levels and clinically diagnosed OA (OR = 0.880, 95% CI 0.626, 1.236, P = 0.461). Similarly, IVW analysis showed no causal association between circulating alpha-tocopherol levels and self-reported OA (OR = 0.980, 95% CI 0.954, 1.006, P = 0.139). Other methods of MR analyses and sensitivity analyses revealed consistent findings. MR-Egger and IVW methods indicated no significant heterogeneity between IVs. The MR-Egger intercept showed no horizontal pleiotropic. The results of this linear Mendelian randomization study indicate no causal association between genetically predicted alpha-tocopherol levels and the progression of OA. Alpha-tocopherol may not provide beneficial and more favorable outcomes for the progression of OA. Further MR analysis based on updated GWASs with more IVs is required to verify the results of our study.
先前的流行病学研究表明，维生素 E 状态与骨关节炎（OA）之间的因果关系仍存在争议。我们采用孟德尔随机化（MR）分析来探讨循环α-生育酚水平（我们体内维生素 E 的主要形式）与 OA 之间的因果关系。循环α-生育酚水平的工具变量（IVs）来自于欧洲血统的 7781 个人的全基因组关联研究（GWAS）数据集。OA 的结果来自英国生物银行。两样本 MR 分析用于估计循环α-生育酚水平与 OA 之间的因果关系。反方差加权（IVW）法是该分析的主要方法。我们在这项工作中使用 MR-Egger 法来确定水平多效性。工具性 IVs 的异质性效应通过 MR-Egger 和 IVW 分析来检测。通过逐个删除单核苷酸多态性（SNP）来进行敏感性分析。在这项分析中，使用了与循环α-生育酚水平强烈相关的三个 SNP（rs964184、rs2108622 和 rs11057830）（P<0.0001）。IVW 随机效应表明，循环α-生育酚水平与临床诊断的 OA 之间没有因果关系（OR=0.880，95%CI 0.626，1.236，P=0.461）。同样，IVW 分析表明，循环α-生育酚水平与自我报告的 OA 之间没有因果关系（OR=0.980，95%CI 0.954，1.006，P=0.139）。其他 MR 分析方法和敏感性分析显示出一致的结果。MR-Egger 和 IVW 方法表明 IVs 之间没有显著的异质性。MR-Egger 截距没有显示水平多效性。这项线性 Mendelian 随机化研究的结果表明，遗传预测的α-生育酚水平与 OA 的进展之间没有因果关系。α-生育酚可能不会为 OA 的进展提供有益和更有利的结果。需要基于具有更多 IVs 的更新 GWAS 进行进一步的 MR 分析，以验证我们研究的结果。
