Association between leukocyte telomere length and cataracts: a bidirectional Mendelian randomization study
CHEN Rong1, Mokoumani2, KE Xiaohong3, WANG Chuhuai1
1. Department of Rehabilitation Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510030, China; 2. The People's Hospital of Leshan Shizhong District, Leshan, Sichuan 614000, China; 3. Sun Yat-sen University, Guangzhou, Guangdong 510030, China
Abstract:Objective To examine the association between leukocyte telomere length and cataract using bidirectional Mendelian randomization (MR) approach, so as to provide the basis for early diagnosis and prevention of cataracts. Methods Leukocyte telomere length data were collected through a meta analysis of genome-wide association studies (GWAS), including 78 952 participants, and the GWAS data of cataract were collected through the UK Biobank, including 8 890 cases and 454 120 controls. A bidirectional MR analysis was performed using the inverse-variance weighted (IVW) method, and single nucleotide polymorphisms (SNPs) which were associated with leukocyte telomere length were selected as instrumental variables. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-Egger regression and the outlier was verified with the leave-one-out and MR-PRESSO test. Results Forward MR analysis results showed that shortened leukocyte telomere length had an increased risk of cataract (OR=0.991, 95%CI: 0.990-0.997). Reverse MR analysis results showed no statistically significant association between leukocyte telomere length and cataract (P>0.05). Cochran's Q test detected no heterogeneity, and neither the MR-Egger regression nor the MR-PRESSO test revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Conclusion Shorter leukocyte telomere length might be associated with increased risk of cataract.
[1] LIU Y C,WILKINS M,KIM T,et al.Cataracts[J].Lancet,2017,390(10094):600-612. [2] 王倩倩,章涛,李傅冬,等.老年人群白内障的影响因素分析[J].预防医学,2023,35(4):311-315. [3] ZHU X J,LI D,DU Y,et al.DNA hypermethylation-mediated downregulation of antioxidant genes contributes to the early onset of cataracts in highly myopic eyes[J].Redox Biol,2018,19:179-189. [4] CHAKRAVARTI D,LABELLA K A,DEPINHO R A.Telomeres:history,health,and hallmarks of aging[J].Cell,2021,184(2):306-322. [5] SANDERS J L,IANNACCONE A,BOUDREAU R M,et al.The association of cataract with leukocyte telomere length in older adults:defining a new marker of aging[J].J Gerontol A Biol Sci Med Sci,2011,66(6):639-645. [6] WANG Y H,LIU Z Y,HUANG C,et al.Analysis of lens epithelium telomere length in age-related cataract[J/OL].Exp Eye Res,2020,201[2024-05-16].https://doi.org/10.1016/j.exer.2020.108279. [7] LI C,STOMA S,LOTTA L A,et al.Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length[J].Am J Hum Genet,2020,106(3):389-404. [8] 梁伟,贡欣,张晓晓,等.子宫内膜癌与乳腺癌的双向孟德尔随机化研究[J].预防医学,2024,36(4):350-354. [9] SKRIVANKOVA V W,RICHMOND R C,WOOLF B A R,et al.Strengthening the reporting of observational studies in epidemiology using mendelian randomization:the STROBE-MR Statement[J].JAMA,2021,326(16):1614-1621. [10] YUAN S,WOLK A,LARSSON S C.Metabolic and lifestyle factors in relation to senile cataract:a Mendelian randomization study[J].Sci Rep,2022,12(1):1-7. [11] LI L,WAN X H,ZHAO G H.Meta-analysis of the risk of cataract in type 2 diabetes[J].BMC Ophthalmol,2014,14:1-8. [12] YU X N,LYU D N,DONG X R,et al.Hypertension and risk of cataract:a meta-analysis[J/OL].PLoS One,2014,9(12)[2024-05-16].https://doi.org/10.1371/journal.pone.0114012. [13] LINDBLAD B E,HAKANSSON N,WOLK A.Smoking cessation and the risk of cataract:a prospective cohort study of cataract extraction among men[J].JAMA Ophthalmol,2014,132(3):253-257. [14] 李红梅,肖倩,谢潇潇,等.肠道微生物与便秘的双向孟德尔随机化研究[J].预防医学,2024,36(3):198-202. [15] BURGESS S,SCOTT R A,TIMPSON N J,et al.Using published data in Mendelian randomization:a blueprint for efficient identification of causal risk factors[J].Eur J Epidemiol,2015,30(7):543-552. [16] BOWDEN J,DAVEY SMITH G,BURGESS S.Mendelian randomization with invalid instruments:effect estimation and bias detection through Egger regression[J].Int J Epidemiol,2015,44(2):512-525. [17] BOWDEN J,DAVEY SMITH G,HAYCOCK P C,et al.Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator[J].Genet Epidemiol,2016,40(4):304-314. [18] HARTWIG F P,DAVEY SMITH G,BOWDEN J.Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption[J].Int J Epidemiol,2017,46(6):1985-1998. [19] VERBANCK M,CHEN C Y,NEALE B,et al.Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J].Nat Genet,2018,50(5):693-698. [20] BABIZHAYEV M A,YEGOROV Y E.Telomere attrition in human lens epithelial cells associated with oxidative stress provide a new therapeutic target for the treatment,dissolving and prevention of cataract with N-acetylcarnosine lubricant eye drops. Kinetic,pharmacological and activity-dependent separation of therapeutic targeting:transcorneal penetration and delivery of L-carnosine in the aqueous humor and hormone-like hypothalamic antiaging effects of the instilled ophthalmic drug through a safe eye medication technique[J].Recent Pat Drug Deliv Formul,2016,10(2):82-129. [21] BABIZHAYEV M A,VISHNYAKOVA K S,YEGOROV Y E.Oxidative damage impact on aging and age-related diseases:drug targeting of telomere attrition and dynamic telomerase activity flirting with imidazole-containing dipeptides[J].Recent Pat Drug Deliv Formul,2014,8(3):163-192. [22] BABIZHAYEV M A,YEGOROV Y E.Biomarkers of oxidative stress and cataract. Novel drug delivery therapeutic strategies targeting telomere reduction and the expression of telomerase activity in the lens epithelial cells with N-acetylcarnosine lubricant eye drops:anti-cataract which helps to prevent and treat cataracts in the eyes of dogs and other animals[J].Curr Drug Deliv,2014,11(1):24-61. [23] BAINS S K,CHAPMAN K,BRIGHT S,et al.Effects of ionizing radiation on telomere length and telomerase activity in cultured human lens epithelium cells[J].Int J Radiat Biol,2019,95(1):54-63.