Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Lipid-Associated Risk Factors for Age-Related Macular Degeneration in the All of Us Research Program
Author Affiliations & Notes
  • Jimmy Chen
    Ophthalmology, University of California at San Diego Department of Ophthalmology at the Shiley Eye Institute, La Jolla, California, United States
  • Sally Liu Baxter
    Ophthalmology, University of California at San Diego Department of Ophthalmology at the Shiley Eye Institute, La Jolla, California, United States
  • Christopher Toomey
    Ophthalmology, University of California at San Diego Department of Ophthalmology at the Shiley Eye Institute, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Jimmy Chen None; Sally Baxter None; Christopher Toomey None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 6167. doi:
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      Jimmy Chen, Sally Liu Baxter, Christopher Toomey; Lipid-Associated Risk Factors for Age-Related Macular Degeneration in the All of Us Research Program. Invest. Ophthalmol. Vis. Sci. 2024;65(7):6167.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age-related macular degeneration (AMD) is the most common cause of vision loss in older patients. Although literature suggests that lipid dysregulation may play a role in AMD pathogenesis, there is no consensus confirming lipid-associated risk factors in AMD. Our study aimed to study lipid-based risk factors for AMD using the All of Us Research Program (AoU).

Methods : All patients who participated in AoU with any stage of AMD, complete demographic data, and available whole genome sequencing (WGS) data were included in this study. A control cohort with no significant eye pathology was age-, race-, ethnicity-, and gender-matched to the AMD cohort in a 2:1 ratio. History of smoking, statin use (including statins hepatically metabolized), and lipid labs including cholesterol and triglycerides were extracted. Additionally, a phenotype of hyperlipidemia (HLD) was created by aggregating labs, medication, and survey data. The presence of Single Nucleotide Polymorphisms (SNPs) associated with AMD and lipid dysregulation such as CFH, ARMS2, LIPC/CETP/LPL, and ApoE were identified from WGS data and analyzed using PLINK. Univariate and multivariable regressions for all extracted variables were then performed to elucidate statistically significant associations with AMD, with statistical significance thresholded at p ≤ 0.05. All statistical analysis was performed using R version 4.0.5.

Results : Overall, 2328 patients with AMD and 5028 matched control patients were included. On univariate analysis, smoking, elevated HDL (high-density lipoproteins), and statin use (especially hepatically metabolized statins) were associated with AMD (p < 0.05 for all variables). On multivariate regression analysis, all significant variables on univariate analysis remained statistically significant (p < 0.05).

Conclusions : Higher HDL levels and use of hepatically metabolized statins appear to be associated with higher AMD prevalence. These findings suggest that elevated systemic HDL levels may contribute to AMD pathogenesis. More work is needed to understand the mechanisms for lipid dysregulation in AMD development.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Table 1. Demographic Variables for the Age-Related Macular Degeneration and Control Cohorts

Table 1. Demographic Variables for the Age-Related Macular Degeneration and Control Cohorts

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