Abstract
Purpose :
Cataract is a leading cause of blindness among the elderly worldwide. Although observational studies have identified clinical and behavioral factors that influence cataract risk, it is not clear if these associations represent causal, modifiable risk factors. We hypothesize that genetically determined primary open-angle glaucoma (POAG), myopic refractive error, type 2 diabetes (T2D), blood pressure, body mass index (BMI), cigarette smoking, and alcohol consumption increase 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 white individuals) 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 refractive error were significantly associated with cataract risk (IVW model: OR [95%CI] =1.04 [1.01-1.08]; P=0.018; and 0.92 [0.89-0.93]; P=6.51x10-13, respectively). Genetically determined T2D was associated with an increased risk of cataract (OR [95%CI] =1.05 [1.01-1.10]; P=0.014). In contrast, genetically determined blood pressure, BMI, cigarette smoking, or alcohol consumption were not associated with cataract risk.
Conclusions :
Our results provide genetic evidence that increased risk for POAG, myopia, or T2D, may be causal risk factors for age-related cataract. These results are consistent with previous observational studies reporting associations of myopia and T2D with cataract risk. This may support population cataract risk stratification and screening strategies, based on ophthalmic conditions information, along with other genetic and clinical information.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.