■先前的观察性研究表明,抗氧化剂失衡与神经退行性疾病有关,虽然其原因尚不清楚。因此,本研究的目的是探索11种抗氧化生物标志物与3种最常见的神经退行性疾病之间的因果关系[阿尔茨海默病(AD),肌萎缩侧索硬化症(ALS)和帕金森病(PD)]。
■进行了双向孟德尔随机化(MR)研究,以使用3种主要方法(方差加权(IVW),加权中位数(WM),和MR-Egger回归)在欧洲人口中。通过最新的全基因组关联研究(GWAS)从开放数据库中获得了11种抗氧化生物标志物的数据,PD和ALS的汇总统计数据来自国际帕金森病基因组学联盟(IPDGC)(33,674例,和449,056个控件),和国际肌萎缩侧索硬化症基因组学联盟(IALSC)(20,806例和59,804例对照),分别。对于AD,我们专门使用了两个最近公布的GWAS数据,一个来自国际阿尔茨海默病基因组学项目(IGAP)(21,982例和41,944例对照),另一个来自大型荟萃分析(71,880例和383,378例对照)作为验证数据。
■基于Bonferroni校正p<0.0015,对神经退行性疾病的抗氧化生物标志物没有显著的因果证据,然而,反向分析发现,AD与视黄醇的减少显着相关(IVW:β=-0.023,p=0.0007;WM:β=-0.025,p=0.0121),虽然在AD验证数据库和视黄醇之间进行了相同的分析,结果一致(IVW:β=-0.064,p=0.025)。此外,谷胱甘肽S-转移酶(GST)的AD,谷胱甘肽过氧化物酶(GPX)上的PD以及尿酸(UA)上的PD也表明了潜在的因果关系(IVW:分别为p=0.025;p=0.027;p=0.021)。
■没有足够的证据表明抗氧化剂失衡对神经退行性疾病具有显着的因果关系。然而,这项研究表明,遗传预测的AD与视黄醇的减少显着相关,这为以前的研究提供了新的见解,并表明将视黄醇视为AD诊断和进展的潜在生物标志物的可能性。
UNASSIGNED: Previous observational studies have suggested that antioxidant imbalance is correlated with neurodegenerative diseases, while its cause-effect remains unclear. Thus, the goal of the present study is to explore the causal relationship between 11 antioxidant biomarkers and 3 most common neurodegenerative diseases [Alzheimer\'s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson\'s disease (PD)].
UNASSIGNED: A bidirectional Mendelian randomization (MR) study was performed to investigate the causal effects by using 3 main methods (Variance Weighted (IVW), Weighted Median (WM), and MR-Egger regression) in the European population. The data of 11 antioxidant biomarkers were obtained from the open database by the most up-to-date Genome-Wide Association Studies (GWAS), the summary statistics of PD and ALS were obtained from the International Parkinson\'s Disease Genomics Consortium (IPDGC) (33,674 cases, and 449,056 controls), and the International Amyotrophic Lateral Sclerosis Genomics Consortium (IALSC) (20,806 cases and 59,804 controls), respectively. For AD, we specifically used two recently published GWAS data, one from the International Genomics of Alzheimer\'s Project (IGAP) (21,982 cases and 41,944 controls), and the other from a large meta-analysis (71,880 cases and 383,378 controls) as validation data.
UNASSIGNED: Based on the Bonferroni correction p < 0.0015, there was no significant causal evidence for the antioxidant biomarkers on neurodegenerative diseases, however, the reverse analysis found that AD was significantly related to the decrease in retinol (IVW: beta = -0.023, p = 0.0007; WM: beta = -0.025, p = 0.0121), while the same analysis was carried out between the AD validation database and retinol, the results were consistent (IVW: beta = -0.064, p = 0.025). Moreover, AD on Glutathione S-transferase (GST), PD on Glutathione Peroxidase (GPX) as well as PD on uric acid (UA) also indicated potential causal-and-effect associations (IVW: p = 0.025; p = 0.027; p = 0.021, respectively).
UNASSIGNED: There was no sufficient evidence that antioxidant imbalance has a significant causal effect on neurodegenerative diseases. However, this study revealed that genetically predicted AD was significantly related to the decrease in retinol, which provides a new insight into previous research and indicates the possibility to regard retinol as potential biomarker for the diagnosis and progress of AD.