Self-reported Myopia and Age-related Cataract: a Two-sample Mendelian Randomization Study

Overview

Journal Sci Rep

Specialty Science

Date 2025 Mar 15

PMID 40087504

Authors

Huan Liu

Feiyan Wang

Jing Wei

Affiliations

Soon will be listed here.

Abstract

Our study aims to investigate whether there is evidence for a causal relationship between self-reported myopia and age-related cataract (ARC). A two-sample Mendelian randomization study was performed to identify the causal associations of self-reported myopia with ARC. We used summary-level genetic association data from the MR-Base (Mendelian Randomization-Base) platform on self-reported myopia and ARC. 26 single-nucleotide polymorphisms (SNPs) associated with self-reported myopia were used as instrumental variables. The inverse-variance weighted (IVW) method was applied to perform the primary analysis, and the weighted median method, MR-Egger regression, and Maximum likelihood methods were selected as supplementary analysis. To ensure the reliability of the results, we also performed the sensitivity analysis and MR-PRESSO analysis to assess the heterogeneity and horizontal pleiotropy. Our results provided evidence for a causal effect of self-reported myopia on ARC risk (IVW: OR 10.657, 95% CI (3.175-35.776), P < 0.001). The results of the weighted median method, MR-Egger regression and Maximum likelihood methods were consistent with the result of the IVW method. No evidence of heterogeneity and horizontal pleiotropy was found by the sensitivity analysis and MR-PRESSO analysis. This study demonstrated that self-reported myopia increases the risk of ARC and provided evidence to support public health interventions to prevent the onset and progress of myopia and develop new therapeutic strategies for myopia. Further large-scale prospective studies are required to validate our findings.

References

Asbell P, Dualan I, Mindel J, Brocks D, Ahmad M, Epstein S . Age-related cataract. Lancet. 2005; 365(9459):599-609. DOI: 10.1016/S0140-6736(05)17911-2. View

Bourne R, Stevens G, White R, Smith J, Flaxman S, Price H . Causes of vision loss worldwide, 1990-2010: a systematic analysis. Lancet Glob Health. 2014; 1(6):e339-49. DOI: 10.1016/S2214-109X(13)70113-X. View

Wallman J, Winawer J . Homeostasis of eye growth and the question of myopia. Neuron. 2004; 43(4):447-68. DOI: 10.1016/j.neuron.2004.08.008. View

Vitale S, Sperduto R, Ferris 3rd F . Increased prevalence of myopia in the United States between 1971-1972 and 1999-2004. Arch Ophthalmol. 2009; 127(12):1632-9. DOI: 10.1001/archophthalmol.2009.303. View

Williams K, Verhoeven V, Cumberland P, Bertelsen G, Wolfram C, Buitendijk G . Prevalence of refractive error in Europe: the European Eye Epidemiology (E(3)) Consortium. Eur J Epidemiol. 2015; 30(4):305-15. PMC: 4385146. DOI: 10.1007/s10654-015-0010-0. View

Baird P, Saw S, Lanca C, Guggenheim J, Smith Iii E, Zhou X . Myopia. Nat Rev Dis Primers. 2020; 6(1):99. DOI: 10.1038/s41572-020-00231-4. View

Bez D, Megreli J, Bez M, Avramovich E, Barak A, Levine H . Association Between Type of Educational System and Prevalence and Severity of Myopia Among Male Adolescents in Israel. JAMA Ophthalmol. 2019; 137(8):887-893. PMC: 6547130. DOI: 10.1001/jamaophthalmol.2019.1415. View

Hysi P, Choquet H, Khawaja A, Wojciechowski R, Tedja M, Yin J . Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia. Nat Genet. 2020; 52(4):401-407. PMC: 7145443. DOI: 10.1038/s41588-020-0599-0. View

Ikuno Y . OVERVIEW OF THE COMPLICATIONS OF HIGH MYOPIA. Retina. 2017; 37(12):2347-2351. DOI: 10.1097/IAE.0000000000001489. View

10.

Hugosson M, Ekstrom C . Prevalence and risk factors for age-related cataract in Sweden. Ups J Med Sci. 2020; 125(4):311-315. PMC: 7594726. DOI: 10.1080/03009734.2020.1802375. View

11.

McCarty C, Mukesh B, Fu C, Taylor H . The epidemiology of cataract in Australia. Am J Ophthalmol. 1999; 128(4):446-65. DOI: 10.1016/s0002-9394(99)00218-4. View

12.

Tang Y, Wang X, Wang J, Jin L, Huang W, Luo Y . Risk factors of age-related cataract in a Chinese adult population: the Taizhou Eye Study. Clin Exp Ophthalmol. 2017; 46(4):371-379. DOI: 10.1111/ceo.13040. View

13.

Choquet H, Melles R, Anand D, Yin J, Cuellar-Partida G, Wang W . A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects. Nat Commun. 2021; 12(1):3595. PMC: 8203611. DOI: 10.1038/s41467-021-23873-8. View

14.

Ma X, Jiao X, Ma Z, Hejtmancik J . Polymorphism rs7278468 is associated with Age-related cataract through decreasing transcriptional activity of the CRYAA promoter. Sci Rep. 2016; 6:23206. PMC: 4794711. DOI: 10.1038/srep23206. View

15.

Gu L, Cong P, Ning Q, Jiang B, Wang J, Cui H . The causal mutation in ARR3 gene for high myopia and progressive color vision defect. Sci Rep. 2023; 13(1):8986. PMC: 10238396. DOI: 10.1038/s41598-023-36141-0. View

16.

Swerdlow D, Kuchenbaecker K, Shah S, Sofat R, Holmes M, White J . Selecting instruments for Mendelian randomization in the wake of genome-wide association studies. Int J Epidemiol. 2016; 45(5):1600-1616. PMC: 5100611. DOI: 10.1093/ije/dyw088. View

17.

Burgess S, Daniel R, Butterworth A, Thompson S . Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways. Int J Epidemiol. 2014; 44(2):484-95. PMC: 4469795. DOI: 10.1093/ije/dyu176. View

18.

Pingault J, OReilly P, Schoeler T, Ploubidis G, Rijsdijk F, Dudbridge F . Using genetic data to strengthen causal inference in observational research. Nat Rev Genet. 2018; 19(9):566-580. DOI: 10.1038/s41576-018-0020-3. View

19.

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

20.

Skrivankova V, Richmond R, Woolf B, Davies N, Swanson S, VanderWeele T . Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration. BMJ. 2021; 375:n2233. PMC: 8546498. DOI: 10.1136/bmj.n2233. View