Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-06-15 DOI:10.1016/j.xops.2025.100853

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

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Abstract

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.

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年龄相关性黄斑变性的遗传风险和基于oct的表型关联

目的：发生老年性黄斑变性（AMD）的风险与多种遗传变异有关。我们的目的是评估AMD遗传风险变异与OCT.DesignA回顾性横断面研究检测到的疾病特定特征之间的关系。参与者：来自单一三级转诊中心诊断为AMD的受试者和健康对照者（50岁）。方法对578例与AMD相关的52个单核苷酸多态性进行基因分型分析。加权遗传风险评分（WGRSs）分别计算了参与补体级联、脂质代谢和其他途径的编码蛋白的基因变异。计算所有52个变异的全局WGRS。OCT图像显示典型的结节、视网膜下结节样沉积物、高反射灶（HRF）、完整的视网膜色素上皮和视网膜外萎缩（cRORA）以及黄斑新生血管的存在。主要观察指标：oct检测WGRS与个体遗传风险变异与特定疾病特征的相关性。结果drusen的存在与脂质WGRS呈正相关（r = 0.09, P = 0.02）。Logistic回归分析显示cRORA与补体评分存在相关性(优势比[OR] = 1.25, 95%可信区间[CI] 1.05-1.50；P = 0.01)，以及总体评分(OR = 1.29, 95% CI 1.13-1.46；P & lt;0.001)。回归还显示HRF与年龄相关性黄斑病变易感性2/高温要求A丝氨酸肽酶1变异相关(OR = 1.53, 95% CI 1.03-2.27；P = 0.03)，其他途径评分(OR = 1.94, 95% CI 1.20-3.12；P = 0.007)，总体评分(OR = 1.16, 95% CI 1.00-1.35；P = 0.04)。结论基于风险变异的AMD加权遗传风险评分与特定疾病特征相关。与途径特异性评分相比，全球WGRS的紧密关联表明，多种途径参与特定疾病特征的发展，如cRORA、drusen和HRF。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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