Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration
Purpose: The risk for developing age-related macular degeneration (AMD) is associated with multiple genetic variants. We aim to evaluate the association of AMD genetic risk variants with specific features of the disease detected by OCT. Design: A retrospective cross-sectional study. Participants: Su...
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Elsevier
2025-11-01
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| Series: | Ophthalmology Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666914525001514 |
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| author | Shlomit Jaskoll Yahel Shwartz, MSc Adi Kramer, MSc Sarah Elbaz-Hayoun, PhD Batya Rinsky, PhD Michelle Grunin, PhD Liran Tiosano, MD Jaime Levy, MD Brice Nguedia Vofo, MD, MBA Itay Chowers, MD |
| author_facet | Shlomit Jaskoll Yahel Shwartz, MSc Adi Kramer, MSc Sarah Elbaz-Hayoun, PhD Batya Rinsky, PhD Michelle Grunin, PhD Liran Tiosano, MD Jaime Levy, MD Brice Nguedia Vofo, MD, MBA Itay Chowers, MD |
| author_sort | Shlomit Jaskoll |
| collection | DOAJ |
| description | Purpose: The risk for developing age-related macular degeneration (AMD) is associated with multiple genetic variants. We aim to evaluate the association of AMD genetic risk variants with specific features of the disease detected by OCT. Design: A retrospective cross-sectional study. Participants: Subjects diagnosed with AMD and healthy controls (>50 years of age) from a single tertiary referral center. Methods: Genotyping of 52 single nucleotide polymorphisms associated with AMD was analyzed in 578 patients. Weighted genetic risk scores (WGRSs) were calculated for variants in genes encoding proteins involved in the complement cascade, lipid metabolism, and other pathways, respectively. A global WGRS was calculated for all 52 variants. OCT images were annotated for the presence of typical drusen, subretinal drusenoid deposits, hyperreflective foci (HRF), complete retinal pigmented epithelium and outer retinal atrophy (cRORA), and macular neovascularization. Main Outcome Measures: Association of WGRS and individual genetic risk variants with specific disease features detected by OCT. Results: A positive correlation between the presence of drusen and the lipid WGRS was detected (r = 0.09, P = 0.02). Logistic regression analysis indicated associations between cRORA and the complement score (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.05–1.50; P = 0.01), as well as the global score (OR = 1.29, 95% CI 1.13–1.46; P < 0.001). Regression also showed an association of HRF with the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 variant (OR = 1.53, 95% CI 1.03–2.27; P = 0.03), the other pathways score (OR = 1.94, 95% CI 1.20–3.12; P = 0.007), and the global score (OR = 1.16, 95% CI 1.00–1.35; P = 0.04). Conclusions: Weighted genetic risk scores based on risk variants for AMD are associated with specific disease features. Tighter association of the global WGRS compared to pathway-specific scores suggests that several pathways are involved in the development of specific disease features such as cRORA, drusen, and HRF. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. |
| format | Article |
| id | doaj-art-14295126849042129dd5ab2fd1dab3d7 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-11-01 |
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| series | Ophthalmology Science |
| spelling | doaj-art-14295126849042129dd5ab2fd1dab3d72025-08-20T03:30:23ZengElsevierOphthalmology Science2666-91452025-11-015610085310.1016/j.xops.2025.100853Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular DegenerationShlomit Jaskoll0Yahel Shwartz, MSc1Adi Kramer, MSc2Sarah Elbaz-Hayoun, PhD3Batya Rinsky, PhD4Michelle Grunin, PhD5Liran Tiosano, MD6Jaime Levy, MD7Brice Nguedia Vofo, MD, MBA8Itay Chowers, MD9The Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel; Faculty of Medicine, Department of Military Medicine and “Tzameret”, Hebrew University of Jerusalem, Jerusalem, Israel, and Medical Corps, Israel Defense Forces, Ramat Gan, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel; Braun School of Public Health, Hebrew University of Jerusalem, Jerusalem, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Faculty of Medicine, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel; Correspondence: Itay Chowers, MD, Department of Ophthalmology, Hadassah - Hebrew University Medical Center, POB 12000, Jerusalem, Israel 91120.Purpose: The risk for developing age-related macular degeneration (AMD) is associated with multiple genetic variants. We aim to evaluate the association of AMD genetic risk variants with specific features of the disease detected by OCT. Design: A retrospective cross-sectional study. Participants: Subjects diagnosed with AMD and healthy controls (>50 years of age) from a single tertiary referral center. Methods: Genotyping of 52 single nucleotide polymorphisms associated with AMD was analyzed in 578 patients. Weighted genetic risk scores (WGRSs) were calculated for variants in genes encoding proteins involved in the complement cascade, lipid metabolism, and other pathways, respectively. A global WGRS was calculated for all 52 variants. OCT images were annotated for the presence of typical drusen, subretinal drusenoid deposits, hyperreflective foci (HRF), complete retinal pigmented epithelium and outer retinal atrophy (cRORA), and macular neovascularization. Main Outcome Measures: Association of WGRS and individual genetic risk variants with specific disease features detected by OCT. Results: A positive correlation between the presence of drusen and the lipid WGRS was detected (r = 0.09, P = 0.02). Logistic regression analysis indicated associations between cRORA and the complement score (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.05–1.50; P = 0.01), as well as the global score (OR = 1.29, 95% CI 1.13–1.46; P < 0.001). Regression also showed an association of HRF with the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 variant (OR = 1.53, 95% CI 1.03–2.27; P = 0.03), the other pathways score (OR = 1.94, 95% CI 1.20–3.12; P = 0.007), and the global score (OR = 1.16, 95% CI 1.00–1.35; P = 0.04). Conclusions: Weighted genetic risk scores based on risk variants for AMD are associated with specific disease features. Tighter association of the global WGRS compared to pathway-specific scores suggests that several pathways are involved in the development of specific disease features such as cRORA, drusen, and HRF. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S2666914525001514Age-related macular degenerationGenetic risk scorePhenotype |
| spellingShingle | Shlomit Jaskoll Yahel Shwartz, MSc Adi Kramer, MSc Sarah Elbaz-Hayoun, PhD Batya Rinsky, PhD Michelle Grunin, PhD Liran Tiosano, MD Jaime Levy, MD Brice Nguedia Vofo, MD, MBA Itay Chowers, MD Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration Ophthalmology Science Age-related macular degeneration Genetic risk score Phenotype |
| title | Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration |
| title_full | Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration |
| title_fullStr | Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration |
| title_full_unstemmed | Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration |
| title_short | Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration |
| title_sort | genetic risk and oct based phenotypic associations in age related macular degeneration |
| topic | Age-related macular degeneration Genetic risk score Phenotype |
| url | http://www.sciencedirect.com/science/article/pii/S2666914525001514 |
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