Synergistic Impact of Clonal Hematopoiesis and Genetic Predisposition on Age-Related Macular Degeneration Risk: Insights from a Large UK Biobank Cohort

Highlight

• Clonal hematopoiesis of indeterminate potential (CHIP) independently elevates the risk of incident age-related macular degeneration (AMD) by 14%.
• Mutations in DNMT3A, spliceosome, and DNA damage repair genes notably contribute to heightened AMD risk.
• A high polygenic risk score (PRS) for AMD synergistically interacts with CHIP, leading to a more than threefold increased risk of AMD.
• The interplay between CHIP and genetic predisposition is particularly pronounced in older adults, suggesting age-related amplification of these risk factors.

Study Background