Table_1_Bidirectional two-sample Mendelian randomization analysis identifies causal associations between oxidative stress and Parkinson’s disease.docx

BackgroundObservational studies have shown that oxidative stress (OS) is associated with Parkinson’s disease (PD). However, whether such observations reflect cause–effect remains largely unknown. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal-effects between OS biomarkers and PD.MethodsWe selected summary statistics data for single-nucleotide polymorphisms (SNPs) associated with catalase (n = 13), glutathione peroxidases (n = 12), superoxide dismutase (n = 13), vitamin A (n = 7), vitamin C (n = 10), vitamin E (n = 12), vitamin B12 (n = 8), folate (n = 14), copper (n = 6), Zinc (n = 7), and iron (n = 23) levels, and the corresponding data for PD from the International Parkinson Disease Genomics Consortium (IPDGC, 33,674 cases and 449,056 controls). Inverse-variance weighted (IVW) MR analyses were conducted to estimate associations of OS with PD. Reverse MR analysis was further performed to predict the causal effects of PD on the above OS biomarkers.ResultsAs for PD, the IVW method suggested that the Zinc (Zn) levels was significantly associated with PD (OR = 1.107, 95% CI 1.013–1.211; p = 0.025), which is consistent with results from the weighted median analyses. Moreover, the results remained consistent and robust in the sensitivity analysis. However, there were no significant associations of catalase, glutathione peroxidases, superoxide dismutase, vitamin A, vitamin C, vitamin E, vitamin B12, folate, copper, or iron with PD. As for OS, our reverse MR analysis also did not support a causal effect of liability to PD on OS.ConclusionThe MR study supported the causal effect of Zn on PD. These findings may inform prevention strategies and interventions directed toward OS and PD.

背景：观察性研究表明，氧化应激（OS）与帕金森病（PD）相关。然而，此类观察是否反映了因果关系尚不清楚。为此，我们进行了一项双向样本孟德尔随机化（MR）分析，以探究OS生物标志物与PD之间的因果效应。方法：我们选取了与过氧化氢酶（n = 13）、谷胱甘肽过氧化物酶（n = 12）、超氧化物歧化酶（n = 13）、维生素A（n = 7）、维生素C（n = 10）、维生素E（n = 12）、维生素B12（n = 8）、叶酸（n = 14）、铜（n = 6）、锌（n = 7）和铁（n = 23）水平相关的单核苷酸多态性（SNPs）的汇总统计数据，以及来自国际帕金森病基因组联盟（IPDGC，病例数33,674例，对照数449,056例）的PD相关数据。通过逆方差加权（IVW）MR分析来估计OS与PD之间的关联。进一步进行了逆MR分析，以预测PD对上述OS生物标志物的因果效应。结果：针对PD，IVW方法表明锌（Zn）水平与PD显著相关（OR = 1.107，95% CI 1.013–1.211；p = 0.025），这与加权中位数分析的结果一致。此外，在敏感性分析中，结果保持一致且稳健。然而，过氧化氢酶、谷胱甘肽过氧化物酶、超氧化物歧化酶、维生素A、维生素C、维生素E、维生素B12、叶酸、铜或铁与PD之间均无显著关联。至于OS，我们的逆MR分析也不支持PD易感性对OS的因果效应。结论：MR研究支持了锌对PD的因果效应。这些发现可能为针对OS和PD的预防策略和干预措施提供信息。