Association of age-related macular degeneration with exposome related metabolomics.

<h4>Introduction</h4>Age-related macular degeneration (AMD) is a multifactorial disease, but it remains unclear how external exposures - the exposome - promote its development. Metabolomics can provide insights to better understand AMD pathophysiology. Previous work to date has focused primarily on associations between endogenous metabolites and AMD.<h4>Objectives</h4>This study aimed for the first time to investigate associations of exogenous metabolites in plasma and urine and AMD.<h4>Methods</h4>Cross-sectional study including patients with AMD and a control group (> 50 years) from Boston, US and Coimbra, Portugal (PT). Color fundus photographs (CFP) of all participants were used for AMD staging. Fasting plasma and urine samples were used for metabolomic profiling using Ultrahigh Performance Liquid Chromatography - Mass Spectrometry (Metabolon, Inc). Multivariate and ordinal logistic mixed-effect regression models were computed for each cohort and then combined by meta-analysis. Primary outcome was association of metabolites with AMD (vs. no AMD). False discovery rate (FDR) was used to account for multiple comparisons and significant q-values are reported.<h4>Results</h4>We included 1023 eyes (823 from the US and 580 from PT). Meta-analysis revealed significant associations of tartronate, thioproline and 2-methoxyhydroquinone sulfate levels with both presence and staging of AMD (q < 0.005 for all). Similar trends were seen in urine.<h4>Conclusion</h4>To the best of our knowledge, this is the first study to identify associations between exogenous metabolites and AMD. These findings are crucial for identifying possible targets for preventive strategies for this blinding disease.