(P41-10-26) Associations Between ARMS2 and CFH Polymorphisms, Micronutrients and Eye Measures: Photoreceptor and Macular Thickness

Objectives: Decreased thickness of the macula and the photoreceptor segment (PS), which is part of the macula, have been associated with age-related macular degeneration (AMD). Both genetics and micronutrients contribute to incident AMD. This study examined if dietary micronutrients, prominent AMD-associated single-nucleotide polymorphisms (SNPs), and their interactions are associated with differences in macular and PS thickness.

Methods: This cross-sectional study used the UK Biobank: a cohort of adults aged from 40-69 years old at enrollment. The predictors in this study were 23 dietary micronutrients (vitamins A, B1, B2, B3, B5, B6, B7, B9, B12, C, D, E, total carotenoids, calcium, magnesium, zinc, manganese, copper, iodine, selenium, and total, heme, and non-heme iron) and three SNPs: ARMS2 rs10490924 and CFH rs3766405 and rs412852. PS and macular layer thickness (outcomes) were derived using retinal optical coherence tomography and averaged between right and left eyes. Micronutrient intakes were calculated via the Oxford WebQ 24-hour recall. Analyses were conducted using linear regression in R, and accounted for sex, energy intake, income, education, socioeconomic status, age, age-squared, body mass index, alcohol intake, smoking status, and the first 10 genetic principal components. Subjects with missing eye measures, nutrient records, SNP genotypes, or covariates were excluded. Analyses were adjusted for false discovery rate (FDR) using the Benjamini-Hochberg method. Significance was set at FDR < 0.05.

Results: After exclusions there were 17,784 subjects. ARMS2 rs10490924 and CFH rs3766405 and rs412852 were associated with decreased PS thickness (FDR < 0.0001). Magnesium, manganese and calcium were associated with increased macular thickness whereas heme iron was associated with a decrease (FDR < 0.05). There were no micronutrient-SNP interactions.

Conclusions: Associations between genotypes and micronutrients were not consistent across the two eye measures, with PS thickness being associated with the three SNPs, while macular thickness was associated with diet. Our results suggest that micronutrient associations with macular thickness may be due to changes in regions other than the PS layer, and that dietary, genetic and interaction effects should be examined in other segments of the macula.

Funding Sources: Not applicable