The causal effect of oxidative stress on the risk of glaucoma
Ronghua Shi,
Yaxuan Wu,
He Chen,
Zicheng Zhang,
Siqi Bao,
Jia Qu,
Meng Zhou
Affiliations
Ronghua Shi
School of Biomedical Engineering, School of Information and Communication Engineering, Hainan University, Haikou 570228, China; Hainan Institute of Real World Data, Qionghai, 571437, China
Yaxuan Wu
School of Biomedical Engineering, School of Information and Communication Engineering, Hainan University, Haikou 570228, China; Hainan Institute of Real World Data, Qionghai, 571437, China
He Chen
School of Biomedical Engineering, School of Information and Communication Engineering, Hainan University, Haikou 570228, China; Hainan Institute of Real World Data, Qionghai, 571437, China
Zicheng Zhang
School of Biomedical Engineering, School of Information and Communication Engineering, Hainan University, Haikou 570228, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Hainan Institute of Real World Data, Qionghai, 571437, China
Siqi Bao
School of Biomedical Engineering, School of Information and Communication Engineering, Hainan University, Haikou 570228, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Hainan Institute of Real World Data, Qionghai, 571437, China
Jia Qu
School of Biomedical Engineering, School of Information and Communication Engineering, Hainan University, Haikou 570228, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Hainan Institute of Real World Data, Qionghai, 571437, China; Corresponding author. School of Biomedical Engineering, School of Information and Communication Engineering, Hainan University, Haikou 570228, China.
Meng Zhou
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; Corresponding author.
Glaucoma is a complex multifactorial disease. Oxidative stress has been implicated in its pathogenesis. However, establishing a causal relationship between oxidative stress and glaucoma is challenging due to confounding and reverse causality. In this study, we performed bidirectional two-sample Mendelian randomization (MR) analyses based on genetic instrumental variables as proxies for 11 biomarkers of oxidative stress injury to investigate the causal relationship between oxidative stress and glaucoma. Eight significant associations were identified. Increased circulating levels of catalase (OR = 0.915, 95 % CI: 0.848–0.987, P = 0.022), retinol (OR = 0.481, 95 % CI: 0.248–0.932, P = 0.044) and superoxide dismutase (OR = 0.779, 95 % CI: 0. 616-0.986, P = 0.038) are associated with a decreased risk of glaucoma, whereas an increased myeloperoxidase level (OR = 2.145, 95 % CI: 1.119–4.111, P = 0.029) is associated with an increased risk of glaucoma. Glaucoma was causally associated with lower levels of total bilirubin (OR = 0.961, 95 % CI: 0.927–0.997, P = 0.039), glutathione peroxidase (OR = 0. 934, 95 % CI: 0.890–0.981, P = 0.006), paraoxonase (OR = 0.883, 95 % CI: 0.810–0.963, P = 0.005) and albumin (OR = 0.988, 95 % CI: 0.978–0.998, P = 0.014). The bidirectional MR analysis revealed a causal relationship between oxidative stress and glaucoma. These findings provide a greater understanding of the underlying mechanisms of glaucomatous neurodegeneration and imply a potential therapeutic approach for glaucoma through targeting oxidative stress pathways.
