AI Article Synopsis
- The study aims to determine how rare dysfunctional genetic variants relate to the progression of advanced age-related macular degeneration (AAMD) in older adults.
- Participants included White patients aged 55-80 without AAMD at the start, followed over a mean of 8-9 years, analyzing genetic and demographic factors.
- Results show that carriers of rare genetic variants had a significantly higher risk of progressing to AAMD, geographic atrophy (GA), and neovascular disease (NV) compared to non-carriers, highlighting the impact of genetics on eye health.
Article Abstract
Purpose: To evaluate associations between rare dysfunctional () genetic variant status and progression to advanced age-related macular degeneration (AAMD), geographic atrophy (GA), and neovascular disease (NV).
Design: Prospective, longitudinal study.
Participants: Patients aged 55 to 80 years at baseline identifying as White with non-AAMD in 1 or both eyes at baseline were included. Follow-up grades were assigned as early, intermediate, or AAMD (GA or NV). variants were categorized using genotyping and sequencing platforms.
Methods: Analyses were performed using the Seddon Longitudinal Cohort Study (N = 2116 subjects, 3901 eyes, and mean follow-up of 8.3 years) and the Age-Related Eye Disease Study (N = 2837 subjects, 5200 eyes, and mean follow-up of 9.2 years). rare variants associated with low serum factor I (FI) protein levels and decreased FI function (type 1), other AMD genetic variants, and demographic, behavioral, and ocular factors were evaluated. Generalized estimating equations methods were used to assess the association between rare variants and progression, independent of other genetic variants and covariates.
Main Outcome Measures: Progression to AAMD, GA, or NV.
Results: In the prospective cohort of 4953 subjects (9101 eyes with non-AAMD at baseline), 1% were type 1 rare carriers. Over 12 years, progression to AAMD was 44% for carriers and 20% for noncarriers ( < 0.001), 30% of carriers versus 10% of noncarriers progressed to GA ( < 0.001), and 18% of carriers compared with 11% of noncarriers progressed to NV ( = 0.049). carriers were more likely to have a family history of AMD ( for trend = 0.035) and a higher baseline AMD grade ( < 0.001). After adjusting for all covariates, carrier status was associated with progression to GA (odds ratio [OR] = 1.91; 95% confidence interval [CI] = 1.03, 3.52) but not NV (OR = 0.96). Higher body mass index was associated with progression among carriers (body mass index ≥ 25 vs. < 25; OR = 5.8; 95% CI 1.5, 22.3) but not for noncarriers (OR = 1.1; 95% CI = 0.9, 1.3), with P_interaction = 0.011.
Conclusions: Results suggest that carriers of rare dysfunctional type 1 variants are at higher risk for progression to AAMD with GA.
Financial Disclosures: Proprietary or commercial disclosure may be found after the references.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993025 | PMC |
| http://dx.doi.org/10.1016/j.xops.2022.100265 | DOI Listing |
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