Blood DNA methylation at AMD candidate loci in discordant monozygotic twins

Abstract

Abstract Age-related macular degeneration (AMD) is a leading cause of visual impairment in older adults, with both genetic and environmental factors contributing to disease risk. Epigenetic mechanisms, particularly DNA methylation, may mediate the effects of environmental exposures on disease-relevant genes, yet their role in AMD remains poorly understood. To investigate blood DNA methylation differences associated with AMD severity, we studied 29 monozygotic twin pairs discordant for AMD from the Finnish Twin Cohort. This design controls for genetic background, sex, age, and shared early-life environment. Genome-wide DNA methylation was measured in whole blood using the Illumina HumanMethylation EPIC BeadChip. Analyses were restricted to 263 AMD candidate genes identified through prior genetic, epigenetic, and transcriptomic studies. Of 9,694 analyzed CpG sites, one site within ESYT1 reached statistical significance after multiple testing correction, but the corresponding methylation difference was below our predefined threshold for biological relevance. No CpG sites met both statistical and biological significance criteria. These findings do not provide evidence for large, systemic DNA methylation differences in peripheral blood at established AMD loci, though subtle effects below the detection limit of the current sample size cannot be excluded.