Associations Between Shorter Leucocyte Telomere Length and Increased Risk of Age-related Macular Degeneration in Women: Insights from the United Kingdom Biobank Study

Objectives: To determine the association between telomere length (TL) and age-related macular degeneration (AMD) and examine the potential variations with sex and ethnicity.

Methods: Population-based, cross-sectional study. A total of 52,083 participants from the UK Biobank were included. Leucocyte TL, measured using quantitative polymerase chain reaction assay, was presented as the ratio of telomere repeat copy number relative to that of a single copy gene, and then log-transformed and Z-standardised. AMD cases were identified based on a combination of in-patient, self-reported and primary care data, and furtherly classified as early, intermediate and late AMD using the Beckmann classification system (based on more severe eye).

Results: Among the 52,083 participants aged 60.2 ± 5.4 years, 725 were any-AMD cases. AMD patients had shorter TL than those without AMD (-0.22 ± 0.95 vs. -0.10 ± 0.99, P = 0.001). In multivariable model, shorter TL (per standard deviation) was significantly associated with higher odds of AMD in Whites (OR:1.09; 95% CI: 1.01-1.18; P = 0.036). When stratified by sex and ethnicity, this association was only significant in White women (OR:1.14; 95%CI: 1.02, 1.27; P = 0.018), but not in men and nonwhite populations (all P ≥ 0.335). Among white women, the association was more pronounced (OR:1.47; 95%CI:1.23-1.77; P < 0.001) for intermediate/late AMD but not for early AMD (P = 0.789).

Conclusions: Shorter TL was associated with any AMD in white women but not in men and other ethnicities. Our findings highlight the potential role of telomere length in the pathogenesis of AMD and the importance of considering sex and ethnicity variation in this research area.