Jaskoll Shlomit, Shwartz Yahel, Kramer Adi, Elbaz-Hayoun Sarah, Rinsky Batya, Grunin Michelle, Tiosano Liran, Levy Jaime, Vofo Brice Nguedia, Chowers Itay
The 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, Israel.
Ophthalmol Sci. 2025 Jun 15;5(6):100853. doi: 10.1016/j.xops.2025.100853. eCollection 2025 Nov-Dec.
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.
A retrospective cross-sectional study.
Subjects diagnosed with AMD and healthy controls (>50 years of age) from a single tertiary referral center.
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.
Association of WGRS and individual genetic risk variants with specific disease features detected by OCT.
A positive correlation between the presence of drusen and the lipid WGRS was detected ( = 0.09, = 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; = 0.01), as well as the global score (OR = 1.29, 95% CI 1.13-1.46; < 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; = 0.03), the other pathways score (OR = 1.94, 95% CI 1.20-3.12; = 0.007), and the global score (OR = 1.16, 95% CI 1.00-1.35; = 0.04).
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.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
发生年龄相关性黄斑变性（AMD）的风险与多种基因变异有关。我们旨在评估AMD基因风险变异与通过光学相干断层扫描（OCT）检测到的该疾病特定特征之间的关联。
一项回顾性横断面研究。
来自单一三级转诊中心的被诊断为AMD的受试者和健康对照（年龄>50岁）。
对578例患者中与AMD相关的52个单核苷酸多态性进行基因分型分析。分别计算参与补体级联反应、脂质代谢和其他途径的蛋白质编码基因变异的加权遗传风险评分（WGRS）。计算所有52个变异的总体WGRS。对OCT图像标注是否存在典型玻璃膜疣、视网膜下玻璃膜疣样沉积物、高反射灶（HRF）、完全视网膜色素上皮和外层视网膜萎缩（cRORA）以及黄斑新生血管。
WGRS和个体遗传风险变异与通过OCT检测到的特定疾病特征之间的关联。
检测到玻璃膜疣的存在与脂质WGRS之间呈正相关（r = 0.09，P = 0.02）。逻辑回归分析表明cRORA与补体评分之间存在关联（比值比[OR] = 1.25，95%置信区间[CI] 1.05 - 1.50；P = 0.01），以及与总体评分之间存在关联（OR = 1.29，95% CI 1.13 - 1.46；P < 0.001）。回归分析还显示HRF与年龄相关性黄斑病变易感性2/高温需求A丝氨酸蛋白酶1变异之间存在关联（OR = 1.53，95% CI 1.03 - 2.27；P = 0.03），与其他途径评分之间存在关联（OR = 1.94，95% CI 1.20 - 3.12；P = 0.007），以及与总体评分之间存在关联（OR = 1.16，95% CI 1.00 - 1.35；P = 0.04）。
基于AMD风险变异的加权遗传风险评分与特定疾病特征相关。与特定途径评分相比，总体WGRS的关联更紧密，这表明多种途径参与了诸如cRORA、玻璃膜疣和HRF等特定疾病特征的发生发展。
在本文末尾的脚注和披露中可能会找到专有或商业披露信息。
