Genetically Determined Physical Activity Levels, Sedentary Behaviours, and Their Association with the Risk of Age-related Macular Degeneration

Overview

Journal J Int Med Res

Publisher Sage Publications

Specialty General Medicine

Date 2025 Feb 14

PMID 39953382

Authors

Xiangpeng Zhou

Jiang Wu

Yingjiao Shen

Shucheng He

Hanyi Guan

Lijun Shen

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the causal effects of physical activity and sedentary traits on risk of Age-related macular degeneration (AMD).

Methods: A two-sample Mendelian randomization (MR) analysis was used to investigate the causal relationship between physical activity and risk of AMD. We used genome-wide association studies (GWAS) summary statistics from two publicly available biobank-scale cohorts: UK Biobank and FinnGen. Physical activity data were self-reported by 703,901 UK Biobank participants and sedentary behaviour data were gathered from 159,606 FinnGen participants. Our analysis primarily used the inverse variance weighted (IVW) method.

Result: Engaging in moderate-to-vigorous physical activity significantly reduced the risk of AMD with an odds ratio of 0.77 (95% CI: 0.66-0.89). However, leisure screen time showed a slight but non-statistically significant upward trend. Sedentary behaviour at work, sedentary commuting showed no causal effects on AMD risk.

Conclusions: This study used MR analysis to examine the causal relationship between physical activity, sedentary behaviour, and AMD. It offers genetic evidence suggesting that physical activity may protect against AMD, emphasizing the significance of lifestyle factors in maintaining ocular health.

References

Wang J, Rochtchina E, Lee A, Chia E, Smith W, Cumming R . Ten-year incidence and progression of age-related maculopathy: the blue Mountains Eye Study. Ophthalmology. 2007; 114(1):92-8. DOI: 10.1016/j.ophtha.2006.07.017. View

Tsao P, Buitrago R, Chan J, Cooke J . Fluid flow inhibits endothelial adhesiveness. Nitric oxide and transcriptional regulation of VCAM-1. Circulation. 1996; 94(7):1682-9. DOI: 10.1161/01.cir.94.7.1682. View

Burgess S, Davey Smith G, Davies N, Dudbridge F, Gill D, Glymour M . Guidelines for performing Mendelian randomization investigations: update for summer 2023. Wellcome Open Res. 2023; 4:186. PMC: 7384151. DOI: 10.12688/wellcomeopenres.15555.3. View

Todoroki T, Takeuchi J, Ota H, Nakano Y, Sajiki A, Nakamura K . Aqueous Humor Cytokine Analysis in Age-Related Macular Degeneration After Switching From Aflibercept to Faricimab. Invest Ophthalmol Vis Sci. 2024; 65(11):15. PMC: 11385661. DOI: 10.1167/iovs.65.11.15. View

Wood A, Guggenheim J . Refractive Error Has Minimal Influence on the Risk of Age-Related Macular Degeneration: A Mendelian Randomization Study. Am J Ophthalmol. 2019; 206:87-93. DOI: 10.1016/j.ajo.2019.03.018. View

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

He M, Xiang F, Zeng Y, Mai J, Chen Q, Zhang J . Effect of Time Spent Outdoors at School on the Development of Myopia Among Children in China: A Randomized Clinical Trial. JAMA. 2015; 314(11):1142-8. DOI: 10.1001/jama.2015.10803. View

Li X, Li H, Cheng J, Wang M, Zhong Y, Shi G . Causal Associations of Thyroid Function and Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study. Am J Ophthalmol. 2022; 239:108-114. DOI: 10.1016/j.ajo.2022.01.026. View

Geenen I, Molin D, van den Akker N, Jeukens F, Spronk H, Schurink G . Endothelial cells (ECs) for vascular tissue engineering: venous ECs are less thrombogenic than arterial ECs. J Tissue Eng Regen Med. 2012; 9(5):564-76. DOI: 10.1002/term.1642. View

10.

Ferris 3rd F, Wilkinson C, Bird A, Chakravarthy U, Chew E, Csaky K . Clinical classification of age-related macular degeneration. Ophthalmology. 2013; 120(4):844-51. PMC: 11551519. DOI: 10.1016/j.ophtha.2012.10.036. View

11.

Sun C, Klein R, Wong T . Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study. Ophthalmology. 2009; 116(10):1913-9. PMC: 3818148. DOI: 10.1016/j.ophtha.2009.03.046. View

12.

Wang Z, Emmerich A, Pillon N, Moore T, Hemerich D, Cornelis M . Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention. Nat Genet. 2022; 54(9):1332-1344. PMC: 9470530. DOI: 10.1038/s41588-022-01165-1. View

13.

Chen X, Hong X, Gao W, Luo S, Cai J, Liu G . Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study. J Transl Med. 2022; 20(1):216. PMC: 9100292. DOI: 10.1186/s12967-022-03407-6. View

14.

Ricci N, Cunha A . Physical Exercise for Frailty and Cardiovascular Diseases. Adv Exp Med Biol. 2020; 1216:115-129. DOI: 10.1007/978-3-030-33330-0_12. View

15.

Colijn J, Meester-Smoor M, Verzijden T, de Breuk A, Silva R, Merle B . Genetic Risk, Lifestyle, and Age-Related Macular Degeneration in Europe: The EYE-RISK Consortium. Ophthalmology. 2020; 128(7):1039-1049. DOI: 10.1016/j.ophtha.2020.11.024. View

16.

Burgess S, Thompson S . Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017; 32(5):377-389. PMC: 5506233. DOI: 10.1007/s10654-017-0255-x. View

17.

Elosua R, Bartali B, Ordovas J, Corsi A, Lauretani F, Ferrucci L . Association between physical activity, physical performance, and inflammatory biomarkers in an elderly population: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2005; 60(6):760-7. DOI: 10.1093/gerona/60.6.760. View

18.

Jingzhi W, Cui X . The Impact of Blood and Urine Biomarkers on Age-Related Macular Degeneration: Insights from Mendelian Randomization and Cross-sectional Study from NHANES. Biol Proced Online. 2024; 26(1):19. PMC: 11201032. DOI: 10.1186/s12575-024-00248-z. View

19.

Timmerman K, Flynn M, Coen P, Markofski M, Pence B . Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise?. J Leukoc Biol. 2008; 84(5):1271-8. DOI: 10.1189/jlb.0408244. View

20.

Yang Q, Sanderson E, Tilling K, Borges M, Lawlor D . Exploring and mitigating potential bias when genetic instrumental variables are associated with multiple non-exposure traits in Mendelian randomization. Eur J Epidemiol. 2022; 37(7):683-700. PMC: 9329407. DOI: 10.1007/s10654-022-00874-5. View