Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, UK.
Sci Rep. 2021 Dec 1;11(1):23255. doi: 10.1038/s41598-021-02631-2.
To evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. UK Biobank participants with no significant ocular history were included using the UK Biobank Resource (project 2112). Spectral-domain optical coherence tomography (SD-OCT) images were taken and segmented to define retinal layers. The influence of AMD risk single-nucleotide polymorphisms (SNP) on retinal layer thickness was analysed. AMD risk associated SNPs were strongly associated with outer-retinal layer thickness. The inner-segment outer segment (ISOS)-retinal pigment epithelium (RPE) thickness measurement, representing photoreceptor outer segments was most significantly associated with the cumulative polygenic risk score, composed of 33 AMD-associated variants, resulting in a decreased thickness (p = 1.37 × 10). Gene-gene interactions involving the NPLOC4-TSPAN10 SNP rs6565597 were associated with significant changes in outer retinal thickness. Thickness of outer retinal layers is highly associated with the presence of risk AMD SNPs. Specifically, the ISOS-RPE measurement. Changes to ISOS-RPE thickness are seen in clinically normal individuals with AMD risk SNPs suggesting structural changes occur at the macula prior to the onset of disease symptoms or overt clinical signs.
评估 AMD 风险基因组变异在正常人群中对黄斑厚度的影响。使用 UK Biobank 资源（项目 2112）纳入无明显眼部病史的 UK Biobank 参与者。进行光谱域光相干断层扫描（SD-OCT）图像采集和分割，以定义视网膜层。分析 AMD 风险单核苷酸多态性（SNP）对视网膜层厚度的影响。与 AMD 相关的风险 SNP 与外视网膜层厚度密切相关。代表光感受器外节的内节-外节（ISOS）-视网膜色素上皮（RPE）厚度测量与由 33 个 AMD 相关变体组成的累积多基因风险评分最显著相关，导致厚度降低（p = 1.37 × 10）。涉及 NPLOC4-TSPAN10 SNP rs6565597 的基因-基因相互作用与外视网膜厚度的显著变化相关。外视网膜层的厚度与 AMD 风险 SNP 的存在高度相关。具体来说，ISOS-RPE 测量。具有 AMD 风险 SNP 的临床正常个体中可见 ISOS-RPE 厚度的变化，表明在疾病症状或明显临床体征出现之前，黄斑区就已经发生了结构变化。
