Investigating the Link between Psychological Well-Being and Early-Stage Age-Related Macular Degeneration: A Mendelian Randomization Analysis.

Purpose: While some studies have started to focus on the link between psychological well-being and age-related macular degeneration (AMD), the relationship remains uncertain. Our research aims to provide new insights into this association, laying a foundation for future interventions and addressing existing knowledge gaps.

Methods: We utilized the "TwoSampleMR" package in R for a bidirectional Mendelian randomization analysis of psychological well-being (subjective well-being, depression, neuroticism, and Sensitivity to Environmental Stress and Adversity) and early-stage AMD. Causal effects were estimated using the inverse-variance weighted method, and additional methods included weighted median and MR-Egger regression. Sensitivity analyses included Cochran's Q test, MR-Egger intercept analysis, MR-PRESSO, and leave-one-out analysis.

Results: The study found that the population with genetic predisposition to neuroticism had a 39.7% lower risk of early-stage AMD (OR = 0.603, 95% CI = 0.385-0.945,  = 0.027). Conversely, the population with genetic predisposition to subjective well-being had a 3.2% increased risk of early-stage AMD (OR = 1.032, 95% CI = 1.003-1.063,  = 0.029). No significant causal relationships were found from depression or Sensitivity to Environmental Stress and Adversity to early-stage AMD, nor from early-stage AMD to psychological well-being.

Conclusion: This study provides preliminary evidence that the relationship between psychological well-being and early-stage AMD may be complex and multifaceted. It suggests that moderate neuroticism levels might reduce early-stage AMD risk through health behaviors, pathophysiological mechanisms, and other factors, while high subjective well-being levels might increase this risk similarly. However, these findings are insufficient for preventive strategies due to a lack of substantial evidence and still require extensive experimental research for further validation.