Abstract：
UNASSIGNED: Oxidative stress (OS) has been linked to neurodegenerative diseases in numerous epidemiological studies; however, whether it is a pathogenesis or a downstream factor remains controversial.
UNASSIGNED: A two-sample bidirectional Mendelian randomization (MR) analysis was implemented to examine evidence of causality of 15 OS injury markers with 3 major neurodegenerative diseases using available genome-wide association studies statistics. As a main approach, inverse-variance weighted (IVW) analysis was performed. The weighted-median (WM) analysis was used to validate the relationship. In order to investigate the existence of horizontal pleiotropy and correct the IVW estimate, the Radial MR approach was applied. To gauge the consistency and robustness of the findings, several sensitivity and pleiotropy analyses were used. For this analysis, p < 0.05 indicates a nominally causal association; according to the Bonferroni correction test, p < 0.0011 indicates a statistically significant causal association.
UNASSIGNED: Via IVW and WM, in directional MR, it was genetically predicted that zinc was nominally causally correlated with the risk of Parkinson\'s disease but not after Bonferroni correction test; alpha-tocopherol was nominally causally correlated with the risk of Amyotrophic lateral sclerosis (ALS) but not after Bonferroni correction test; furthermore, in reverse MR, it was genetically predicted that Alzheimer\'s disease was causally correlated with uric acid but not after Bonferroni correction test. These above findings were stable across sensitivity and pleiotropy analyses.
UNASSIGNED: Based on the current study, there is no authentic genetic causal association between OS biomarkers and neurodegenerative diseases. The complex relationship is required to be confirmed in future experimental research.
UNASSIGNED: A two-sample bidirectional Mendelian randomization (MR) analysis was implemented to examine evidence of causality of 15 OS injury markers with 3 major neurodegenerative diseases using available genome-wide association studies statistics. As a main approach, inverse-variance weighted (IVW) analysis was performed. The weighted-median (WM) analysis was used to validate the relationship. In order to investigate the existence of horizontal pleiotropy and correct the IVW estimate, the Radial MR approach was applied. To gauge the consistency and robustness of the findings, several sensitivity and pleiotropy analyses were used. For this analysis, p < 0.05 indicates a nominally causal association; according to the Bonferroni correction test, p < 0.0011 indicates a statistically significant causal association.
UNASSIGNED: Via IVW and WM, in directional MR, it was genetically predicted that zinc was nominally causally correlated with the risk of Parkinson\'s disease but not after Bonferroni correction test; alpha-tocopherol was nominally causally correlated with the risk of Amyotrophic lateral sclerosis (ALS) but not after Bonferroni correction test; furthermore, in reverse MR, it was genetically predicted that Alzheimer\'s disease was causally correlated with uric acid but not after Bonferroni correction test. These above findings were stable across sensitivity and pleiotropy analyses.
UNASSIGNED: Based on the current study, there is no authentic genetic causal association between OS biomarkers and neurodegenerative diseases. The complex relationship is required to be confirmed in future experimental research.
摘要：
■在许多流行病学研究中，氧化应激（OS）与神经退行性疾病有关；然而，是发病机制还是下游因素仍存在争议。
■实施了双样本双向孟德尔随机化（MR）分析，以使用可用的全基因组关联研究统计数据来检查15种OS损伤标志物与3种主要神经退行性疾病的因果关系。作为一种主要方法，进行逆方差加权(IVW)分析。使用加权中位数(WM)分析来验证该关系。为了研究水平多效性的存在并校正IVW估计，应用了径向MR方法。为了衡量调查结果的一致性和稳健性，使用了几种敏感性和多效性分析。对于这个分析，p<0.05表示名义上的因果关系；根据Bonferroni校正检验，p<0.0011表示统计学上显著的因果关联。
■通过IVW和WM，在定向MR中，根据基因预测，锌与帕金森氏病的风险名义上有因果关系，但在Bonferroni校正试验后没有；α-生育酚与肌萎缩侧索硬化症（ALS）的风险名义上有因果关系，但在Bonferroni校正试验后没有；在反向MR中，根据基因预测，阿尔茨海默病与尿酸有因果关系，但在Bonferroni校正试验后没有。这些上述发现在敏感性和多效性分析中是稳定的。
■根据目前的研究，OS生物标志物与神经退行性疾病之间没有真正的遗传因果关系.复杂的关系需要在未来的实验研究中得到证实。
■实施了双样本双向孟德尔随机化（MR）分析，以使用可用的全基因组关联研究统计数据来检查15种OS损伤标志物与3种主要神经退行性疾病的因果关系。作为一种主要方法，进行逆方差加权(IVW)分析。使用加权中位数(WM)分析来验证该关系。为了研究水平多效性的存在并校正IVW估计，应用了径向MR方法。为了衡量调查结果的一致性和稳健性，使用了几种敏感性和多效性分析。对于这个分析，p<0.05表示名义上的因果关系；根据Bonferroni校正检验，p<0.0011表示统计学上显著的因果关联。
■通过IVW和WM，在定向MR中，根据基因预测，锌与帕金森氏病的风险名义上有因果关系，但在Bonferroni校正试验后没有；α-生育酚与肌萎缩侧索硬化症（ALS）的风险名义上有因果关系，但在Bonferroni校正试验后没有；在反向MR中，根据基因预测，阿尔茨海默病与尿酸有因果关系，但在Bonferroni校正试验后没有。这些上述发现在敏感性和多效性分析中是稳定的。
■根据目前的研究，OS生物标志物与神经退行性疾病之间没有真正的遗传因果关系.复杂的关系需要在未来的实验研究中得到证实。
