Association of Age-Related Cataract Risk with High Polygenetic Risk Scores Involved in Galactose-Related Metabolism and Dietary Interactions

Cataracts are associated with the accumulation of galactose and galactitol in the lens. We determined the polygenetic risk scores for the best model (PRSBM) associated with age-related cataract (ARC) risk and their interaction with diets and lifestyles in 40,262 Korean adults aged over 50 years belonging to a hospital-based city cohort. Methods: The genetic variants for ARC risk were selected in lactose and galactose metabolism-related genes with multivariate logistic regression using PLINK 1.9 version. PRSBM from the selected genetic variants were estimated by generalized multifactor dimensionality reduction (GMDR) after adjusting for covariates. The interactions between the PRSBM and each lifestyle factor were determined to modulate ARC risk. Results: The genetic variants for ARC risk related to lactose and galactose metabolism were SLC2A1 _rs3729548, ST3GAL3 _rs3791047, LCT _rs2304371, GALNT5 _rs6728956, ST6GAL1 _rs2268536, GALNT17 _rs17058752, CSGALNACT1 _rs1994788, GALNTL4 _rs10831608, B4GALT6 _rs1667288, and A4GALT _ rs9623659. In GMDR, the best model included all ten genetic variants. The highest odds ratio for a single SNP in the PRSBM was 1.26. However, subjects with a high-PRSBM had a higher ARC risk by 2.1-fold than a low-PRSBM after adjusting for covariates. Carbohydrate, dairy products, kimchi, and alcohol intake interacted with PRSBM for ARC risk, where participants with high-PRSBM had a much higher ARC risk than those with low-PRSBM when consuming diets with high carbohydrate and low dairy product and kimchi intake. However, only with low alcohol intake, the participants with high-PRSBM had a higher ARC risk than those with low-PRSBM. Conclusion: Adults aged >50 years having high-PRSBM may modulate dietary habits to reduce ARC risk.