Princess Alexandra Eye Pavilion, University of Edinburgh, Edinburgh, UK.
Institute of Health Services Research in Dentistry, University of Münster, Münster, Germany.
Eye (Lond). 2024 Dec;38(17):3347-3351. doi: 10.1038/s41433-024-03303-x. Epub 2024 Aug 15.
The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angle glaucoma (POAG), or if it arises as a consequence of the sequelae of POAG. Therefore, we conducted a Mendelian Randomization (MR) mediation analysis to elucidate the mediating role of POAG in the association between IOP and RVO.
We identified 47 single-nucleotide polymorphisms (SNPs) associated with IOP (P-value < 5 × 10) leveraging data from a genome-wide association study (GWAS) (N = 97,653) obtained from the UK Biobank and 50 SNPs associated with POAG (P-value < 5 × 10) from a GWAS meta-analysis (16,677 cases and 199,580 controls). We related these SNPs with RVO using a GWAS of 775 RVO cases and 376,502 controls from FinnGen. By utilizing univariable and multivariable MR analyses we calculated the total effect of IOP on RVO and estimated the degree to which POAG mediates this association.
MR analyses showed that higher IOP is associated with higher RVO risk (odds ratio of RVO per 1 mmHg increase in IOP: 1.53; 95% confidence interval: 1.04 to 2.26; p-value = 0.03). Moreover, our MR mediation analysis suggested that 91.6% of the total effect of IOP on RVO risk was mediated through POAG. The primary results were consistent with estimates of pleiotropy-robust MR methods.
Our findings suggest that higher IOP increases the risk of RVO and that the majority of this effect is mediated through POAG.
眼内压（IOP）与视网膜静脉阻塞（RVO）风险之间的病因联系仍不清楚，特别是关于这种风险是否源自升高的眼内压（IOP）的直接影响，而与原发性开角型青光眼（POAG）的存在无关，或者是否是 POAG 的后果所致。因此，我们进行了孟德尔随机化（MR）中介分析，以阐明 POAG 在 IOP 与 RVO 之间的关联中的中介作用。
我们利用来自英国生物银行的全基因组关联研究（GWAS）数据（N=97653），确定了 47 个与 IOP 相关的单核苷酸多态性（SNP）（P 值<5×10），并利用 GWAS 荟萃分析中与 POAG 相关的 50 个 SNP（P 值<5×10）（16677 例病例和 199580 例对照）。我们使用来自 FinnGen 的 775 例 RVO 病例和 376502 例对照的 GWAS 将这些 SNP 与 RVO 相关联。通过使用单变量和多变量 MR 分析，我们计算了 IOP 对 RVO 的总效应，并估计了 POAG 对这种关联的中介程度。
MR 分析表明，IOP 升高与 RVO 风险增加相关（IOP 每升高 1mmHg，RVO 的优势比：1.53；95%置信区间：1.04 至 2.26；p 值=0.03）。此外，我们的 MR 中介分析表明，IOP 对 RVO 风险的总效应有 91.6%是通过 POAG 介导的。主要结果与基于不易产生偏倚的 MR 方法的估计值一致。
我们的研究结果表明，IOP 升高会增加 RVO 的风险，而这种效应的大部分是通过 POAG 介导的。
