Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study
AIM: To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration (AMD) phenotypes. METHODS: A bidirectional Mendelian randomization (MR) analytical protocol was implemented, which utilized genome-wide association study (GWAS) summary statistics derived from the IEU...
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Press of International Journal of Ophthalmology (IJO PRESS)
2025-07-01
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| Series: | International Journal of Ophthalmology |
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| Online Access: | http://ies.ijo.cn/en_publish/2025/7/20250714.pdf |
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| author | Li-Yun Yuan Wang-Ming Su Liang-Pin Li Xiao-Feng Tian Xue-Li Zheng Xiao-Yong Yuan |
| author_facet | Li-Yun Yuan Wang-Ming Su Liang-Pin Li Xiao-Feng Tian Xue-Li Zheng Xiao-Yong Yuan |
| author_sort | Li-Yun Yuan |
| collection | DOAJ |
| description | AIM: To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration (AMD) phenotypes. METHODS: A bidirectional Mendelian randomization (MR) analytical protocol was implemented, which utilized genome-wide association study (GWAS) summary statistics derived from the IEU OpenGWAS repositories. The investigation focused on 11 oxidative stress markers and AMD phenotypes, encompassing both wet and dry subtypes. The MR methodology incorporated inverse-variance weighted (IVW) calculations, MR-Egger statistical regression, weighted median approximation, and weighted mode assessments to estimate causative relationships. Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy. RESULTS: Genetically predicted elevated catalase (CAT) concentrations demonstrated significant associations with heightened risks of overall AMD (IVW OR=1.084, 95%CI: 1.021-1.151, P=0.008) and wet AMD phenotype (IVW OR=1.113, 95%CI: 1.047-1.247, P=0.007). Higher genetically predicted albumin concentrations corresponded with reduced AMD risk (IVW OR=0.827, 95%CI: 0.715-0.957, P=0.013) but increased wet AMD risk (IVW OR=1.229, 95%CI: 1.036-1.458, P=0.018). Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels (IVW OR=0.987, 95%CI: 0.979-0.996, P=0.004), while wet AMD corresponded with decreased total bilirubin (TBIL) and paraoxonase (PON) activity. CONCLUSION: The results offer strong support for a causal link between markers of oxidative stress and the development of AMD, indicating that oxidative processes play a role in driving the disease progression. |
| format | Article |
| id | doaj-art-b0ff3bbf0d4c4255adc5a9e99d912114 |
| institution | OA Journals |
| issn | 2222-3959 2227-4898 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
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| series | International Journal of Ophthalmology |
| spelling | doaj-art-b0ff3bbf0d4c4255adc5a9e99d9121142025-08-20T02:36:35ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982025-07-011871307131610.18240/ijo.2025.07.1420250714Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization studyLi-Yun Yuan0Wang-Ming Su1Liang-Pin Li2Xiao-Feng Tian3Xue-Li Zheng4Xiao-Yong Yuan5Xiao-Yong Yuan. School of Medicine, Nankai University, Weijin Road, Nankai District, Tianjin 300071, China; Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, 4 Gansu Road, Heping District, Tianjin 300020, China. yuanxy_cn@hotmail.comOphthalmology Department, The Second Hospital of Longyan, Longyan 364000, Fujian Province, ChinaTianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, ChinaTianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, ChinaDepartment of Ophthalmology, The First People's Hospital of Xianyang, Xianyang 712000, Shaanxi Province, ChinaSchool of Medicine, Nankai University, Tianjin 300071, China; Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, ChinaAIM: To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration (AMD) phenotypes. METHODS: A bidirectional Mendelian randomization (MR) analytical protocol was implemented, which utilized genome-wide association study (GWAS) summary statistics derived from the IEU OpenGWAS repositories. The investigation focused on 11 oxidative stress markers and AMD phenotypes, encompassing both wet and dry subtypes. The MR methodology incorporated inverse-variance weighted (IVW) calculations, MR-Egger statistical regression, weighted median approximation, and weighted mode assessments to estimate causative relationships. Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy. RESULTS: Genetically predicted elevated catalase (CAT) concentrations demonstrated significant associations with heightened risks of overall AMD (IVW OR=1.084, 95%CI: 1.021-1.151, P=0.008) and wet AMD phenotype (IVW OR=1.113, 95%CI: 1.047-1.247, P=0.007). Higher genetically predicted albumin concentrations corresponded with reduced AMD risk (IVW OR=0.827, 95%CI: 0.715-0.957, P=0.013) but increased wet AMD risk (IVW OR=1.229, 95%CI: 1.036-1.458, P=0.018). Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels (IVW OR=0.987, 95%CI: 0.979-0.996, P=0.004), while wet AMD corresponded with decreased total bilirubin (TBIL) and paraoxonase (PON) activity. CONCLUSION: The results offer strong support for a causal link between markers of oxidative stress and the development of AMD, indicating that oxidative processes play a role in driving the disease progression.http://ies.ijo.cn/en_publish/2025/7/20250714.pdfage-related macular degenerationoxidative stressmendelian randomizationantioxidant therapygenetic epidemiologyretinal degeneration |
| spellingShingle | Li-Yun Yuan Wang-Ming Su Liang-Pin Li Xiao-Feng Tian Xue-Li Zheng Xiao-Yong Yuan Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study International Journal of Ophthalmology age-related macular degeneration oxidative stress mendelian randomization antioxidant therapy genetic epidemiology retinal degeneration |
| title | Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study |
| title_full | Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study |
| title_fullStr | Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study |
| title_full_unstemmed | Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study |
| title_short | Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study |
| title_sort | causal role of oxidative stress in age related macular degeneration a bidirectional mendelian randomization study |
| topic | age-related macular degeneration oxidative stress mendelian randomization antioxidant therapy genetic epidemiology retinal degeneration |
| url | http://ies.ijo.cn/en_publish/2025/7/20250714.pdf |
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