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. 2024 May 1;65(5):35.
doi: 10.1167/iovs.65.5.35.

Age-Related Macular Degeneration and Extramacular Drusen: Genetic Associations in the Coimbra Eye Study

Cláudia Farinha  1   2   3   4 , Patrícia Barreto  1 , Rita Coimbra  1   5 , Maria Beatriz Machado  3 , Inês Figueiredo  1   2 , Maria Luz Cachulo  1   2   3   4 , José Cunha-Vaz  1   3   4 , Rufino Silva  1   2   3   4
Affiliations

Age-Related Macular Degeneration and Extramacular Drusen: Genetic Associations in the Coimbra Eye Study

Cláudia Farinha et al. Invest Ophthalmol Vis Sci. .

Abstract

Purpose: To explore the association between the genetics of age-related macular degeneration (AMD) and extramacular drusen (EMD) in patients with and without AMD.

Methods: We included 1753 eyes (912 subjects) with phenotypic characterization regarding AMD and EMD. Genetic sequencing and the genetic risk score (GRS) for AMD were performed according to the EYE-RISK consortium methodology. To test for differences in the GRS from EMD cases, AMD cases, and controls, a clustered Wilcoxon rank-sum test was used. The association of AMD, EMD, and the GRS was evaluated using logistic regression models adjusted for age and sex. Individual associations of common risk variants for AMD with EMD were explored.

Results: EMD were found in 755 eyes: 252 (14.4%) with AMD and 503 (28.7%) without. In total, 122 eyes (7.0%) had only AMD, and 876 (50.0%) were controls. EMD were strongly associated with AMD (odds ratio [OR], 3.333; 95% confidence interval [CI], 2.356-4.623; P < 0.001). The GRS was associated with an increased risk of AMD (OR, 1.416; 95% CI, 1.218-1.646; P < 0.001) but not with EMD. Individually, the common risk variants ARMS2 rs10490924 (P = 0.042), C3 rs2230199 (P = 0.042), and CETP rs5817082 (P = 0.042) were associated with EMD, after adjustment for AMD, sex, and age.

Conclusions: We found a strong association between EMD and AMD, suggesting a common pathogenesis. The GRS for AMD was not associated with EMD, but a partially overlapping genetic basis was suggested when assessing individual risk variants. We propose that EMD per se do not represent an increase in the global genetic risk for AMD.

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Conflict of interest statement

Disclosure: C. Farinha, Novartis (C), Bayer (C), Abbvie (C); P. Barreto, None; R. Coimbra, None; M.B. Machado, None; I. Figueiredo, None; M.L. Cachulo, Bayer (C), Novartis (C); J. Cunha-Vaz, Precision Ocular Ltd (C), Roche (C), Carl Zeiss Meditec (C), AlimeraSciences (C), Allergan (C), Bayer (C), Gene Signal (C), Novartis (C), Pfizer (C), Sanofi-Aventis (C), Vifor Pharma (C); R. Silva, Bayer (C), Alcon (C), Thea (C), Novartis (C), Alimera Sciences (C), Allergan (C)

Figures

Figure 1.
Figure 1.
Flowchart of the participants and included subjects in the analysis.
Figure 2.
Figure 2.
(A) A 71-year-old woman with only EMD, which are mainly located in the superior and nasal retina, and displaying mild features, despite a relatively high GRS for AMD of 3.21 (GRS by pathway = ARMS2 2.15, complement 1.30, lipids –0.27, ECM –0.08). (B) A 64-year-old man with AMD and EMD, displaying more severe features regarding the type, number, and distribution of EMD, and with a high GRS for AMD of 4.12 (GRS by pathway = ARMS2 2.15, complement 1.63, lipids 0.35, ECM –0.02).
Figure 3.
Figure 3.
Distributions of the GRS for controls, eyes with EMD without AMD, eyes with AMD without EMD, and eyes with AMD and EMD.
Figure 4.
Figure 4.
Distribution of the overall GRS between groups, depicting significant overlapping between categories.
See this image and copyright information in PMC

References

    1. Colijn JM, Buitendijk GHS, Prokofyeva E, et al. .. Prevalence of age-related macular degeneration in europe: the past and the future. Ophthalmology. 2017; 124(12): 1753–1763. - PMC - PubMed
    1. Wong WL, Su X, Li X, et al. .. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Global Health. 2014; 2(2): e106–e116. - PubMed
    1. Lambert NG, ElShelmani H, Singh MK, et al. .. Risk factors and biomarkers of age-related macular degeneration. Prog Retin Eye Res. 2016; 54: 64–102. - PMC - PubMed
    1. Fritsche LG, Fariss RN, Stambolian D, Abecasis GR, Curcio CA, Swaroop A.. Age-related macular degeneration: genetics and biology coming together. Annu Rev Genomics Hum Genet. 2014; 15: 151–171. - PMC - PubMed
    1. Fritsche LG, Igl W, Bailey JN, et al. .. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2016; 48(2): 134–143. - PMC - PubMed

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