Association of Behavioral and Clinical Risk Factors With Cataract: A Two-Sample Mendelian Randomization Study

Author(s)Jiang, Chen
Author(s)Melles, Ronald B.
Author(s)Sangani, Poorab
Author(s)Hoffmann, Thomas J.
Author(s)Hysi, Pirro G.
Author(s)Glymour, M. Maria
Author(s)Jorgenson, Eric
Author(s)Lachke, Salil A.
Author(s)Choquet, Hélène
Date Accessioned2023-09-28T19:35:00Z
Date Available2023-09-28T19:35:00Z
Publication Date2023-07
DescriptionThis article was originally published in Investigative Ophthalmology & Visual Science. The version of record is available at: Copyright 2023 The Authors
AbstractPurpose: To investigate the association of genetically determined primary open-angle glaucoma (POAG), myopic refractive error (RE), type 2 diabetes (T2D), blood pressure (BP), body mass index (BMI), cigarette smoking, and alcohol consumption with the risk of age-related cataract. Methods: To assess potential causal effects of clinical or behavioral factors on cataract risk, we conducted two-sample Mendelian randomization analyses. Genetic instruments, based on common genetic variants associated with risk factors at genome-wide significance (P < 5 × 10−8), were derived from published genome-wide association studies (GWAS). For age-related cataract, we used GWAS summary statistics from our previous GWAS conducted in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (28,092 cataract cases and 50,487 controls; all non-Hispanic whites) or in the UK Biobank (31,852 cataract cases and 428,084 controls; all European-descent individuals). We used the inverse-variance weighted (IVW) method as our primary source of Mendelian randomization estimates and conducted common sensitivity analyses. Results: We found that genetically determined POAG and mean spherical equivalent RE were significantly associated with cataract risk (IVW model: odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.01–1.08; P = 0.018; per diopter more hyperopic: OR = 0.92; 95% CI, 0.89–0.93; P = 6.51 × 10−13, respectively). In contrast, genetically determined T2D, BP, BMI, cigarette smoking, or alcohol consumption were not associated with cataract risk (P > 0.05). Conclusions: Our results provide evidence that genetic risks for POAG and myopia may be causal risk factors for age-related cataract. These results are consistent with previous observational studies reporting associations of myopia with cataract risk. This information may support population cataract risk stratification and screening strategies.
SponsorThe authors are grateful to the Kaiser Permanente Northern California members who have generously agreed to participate in the Kaiser Permanente Research Program on Genes, Environment, and Health. Support for participant enrollment, survey completion, and biospecimen collection for the RPGEH was provided by the Robert Wood Johnson Foundation, the Wayne and Gladys Valley Foundation, the Ellison Medical Foundation, and Kaiser Permanente Community Benefit Programs. Genotyping of the GERA cohort was funded by a grant from the National Institute on Aging, National Institute of Mental Health, and National Institute of Health Common Fund (RC2 AG036607). This work was also supported by grants from the National Eye Institute (R01 EY033010 to HC and SAL; R01 EY027004 to HC).
PublisherInvestigative Ophthalmology & Visual Science
Keywordsmendelian randomization
Keywordscataract risk factors
Keywordsgenetic epidemiology
TitleAssociation of Behavioral and Clinical Risk Factors With Cataract: A Two-Sample Mendelian Randomization Study
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