Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443003, China.
Institute of Cardiovascular Diseases, Three Gorges University, Yichang, 443003, China.
Mol Neurobiol. 2024 Dec;61(12):10551-10560. doi: 10.1007/s12035-024-04231-3. Epub 2024 May 16.
The purpose of this study was to investigate the relationship between oxidative stress and cognitive function, encompassing cognitive performance, intelligence, memory, reaction time, speech and vision by a bidirectional Mendelian randomisation study. Independent genetic variants associated with glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), peroxiredoxin (PRDX), sulfhydryl oxidase (SOX) and thyroid peroxidase (TPO) were explored using a genome-wide association study (GWAS). The inverse variance weighted (IVW) or Wald ratio method was employed to ascertain the relationship between antioxidant enzymes and cognitive function. The MR analyses indicated that the MR effect estimates of GST (β = 0.0352, P = 0.0047, FDR = 0.0164) and TPO (β = 0.0531, P = 0.0003, FDR = 0.0021) were significantly associated with cognitive performance elevation. Furthermore, genetically predicted GST (β = 0.0334, P = 0.0043, FDR = 0.0151) and TPO (β = 0.0496, P = 0.0031, FDR = 0.0151) were found to be associated with high intelligence. Additionally, there were also some associations of SOX (β = 0.0243, P = 0.0283, FDR = 0.066) on high cognitive performance, TPO (β = 0.1189, P = 0.0315, FDR = 0.2205) on larger maximum digits remembered correctly, and SOX (β = - 0.2435, P = 0.0395, FDR = 0.1185) on reaction time. Nevertheless, the associations between antioxidant enzymes and speech and linguistic disorders, as well as visual disturbances, were not significant. We did not find reverse causation between antioxidant enzymes and cognitive function traits. This study provides evidence of potential causal relationships between oxidative stress and cognitive function.
本研究旨在通过双向孟德尔随机化研究探讨氧化应激与认知功能的关系，包括认知表现、智力、记忆、反应时间、言语和视觉。使用全基因组关联研究（GWAS）探讨与谷胱甘肽 S-转移酶（GST）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPX）、过氧化物酶（PRDX）、硫氧还蛋白氧化酶（SOX）和甲状腺过氧化物酶（TPO）相关的独立遗传变异。采用逆方差加权（IVW）或 Wald 比值法确定抗氧化酶与认知功能之间的关系。MR 分析表明，GST（β=0.0352，P=0.0047，FDR=0.0164）和 TPO（β=0.0531，P=0.0003，FDR=0.0021）的 MR 效应估计值与认知表现升高显著相关。此外，遗传预测的 GST（β=0.0334，P=0.0043，FDR=0.0151）和 TPO（β=0.0496，P=0.0031，FDR=0.0151）与高智力有关。此外，SOX（β=0.0243，P=0.0283，FDR=0.066）与高认知表现、TPO（β=0.1189，P=0.0315，FDR=0.2205）与正确记住的最大数字增加以及 SOX（β=-0.2435，P=0.0395，FDR=0.1185）与反应时间之间也存在一些关联。然而，抗氧化酶与言语和语言障碍以及视觉障碍之间的关联并不显著。我们没有发现抗氧化酶和认知功能特征之间存在反向因果关系。本研究提供了氧化应激与认知功能之间存在潜在因果关系的证据。
