Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, The People's Republic of China.
Wuhan Aier Eye Hospital of Wuhan University, Wuhan, The People's Republic of China.
Ann Hum Genet. 2024 Jul;88(4):336-348. doi: 10.1111/ahg.12552. Epub 2024 Feb 19.
Increasing evidence implicates retinal vascular occlusions as a susceptibility factor for cardiovascular diseases (CVDs), whereas inconsistent results on the relationship were reported in previous observational studies. This research using a bidirectional two-sample Mendelian randomization (MR) analysis aimed to investigate the potential association between genetically determined central/branch retinal artery and retinal vein occlusions (CRAO/BRAO/RVO) and the risk of CVD.
Summary statistics of retinal vascular occlusions from the largest available genome-wide association study of European descent were used to investigate their relationship with CVDs, and vice versa. Primary analyses were conducted using the common inverse-variance weighted approach. Several complementary sensitivity analyses were performed to verify the reliability of our results.
Inverse variance weighted method showed suggestive effects of genetically determined RVO on ischemic stroke (IS) (odds ratio [OR] = 1.021, 95% confidence [CI] = 1.004-1.037, p = 0.012), a genetic liability to CRAO increased the risk of myocardial infarction (MI) (OR = 1.014, 95% CI = 1.006-1.023, p = 7.0 × 10-4). In addition, genetic predisposition to BRAO had a positive effect on stroke (OR = 1.008, 95% CI = 1.002-1.013, p = 0.011), IS (OR = 1.007, 95% CI = 1.001-1.014, p = 0.022), and cardioembolic stroke (CES) (OR = 1.018, 95% CI = 1.006-1.031, p = 0.004). The point estimates from sensitivity analyses were in the same direction. Reverse MR analyses found no significant evidence for the effect of CVDs on retinal vascular occlusions.
Our MR study provides potential evidence that retinal vascular occlusions are causally linked to increased risk of CVDs including IS, MI, stroke, and CES. This supports the need for clinical CVD screening in individuals with retinal vascular occlusions. Further investigations are warranted to clarify the effects of CVDs on ocular comorbidities.
越来越多的证据表明视网膜血管阻塞是心血管疾病（CVD）的易感因素，而先前的观察性研究报告的两者之间的关系结果并不一致。本研究采用双向两样本孟德尔随机化（MR）分析，旨在探讨遗传决定的中心/分支视网膜动脉和静脉阻塞（CRAO/BRAO/RVO）与 CVD 风险之间的潜在关联。
利用欧洲血统最大的全基因组关联研究中视网膜血管阻塞的汇总统计数据，来研究它们与 CVD 之间的关系，反之亦然。主要分析采用常见的逆方差加权法进行。进行了几种补充敏感性分析，以验证我们结果的可靠性。
逆方差加权法显示，遗传决定的 RVO 与缺血性中风（IS）之间存在提示性关联（比值比[OR] = 1.021，95%置信区间[CI] = 1.004-1.037，p = 0.012），CRAO 的遗传易感性增加了心肌梗死（MI）的风险（OR = 1.014，95%CI = 1.006-1.023，p = 7.0×10-4）。此外，BRAO 的遗传易感性对中风（OR = 1.008，95%CI = 1.002-1.013，p = 0.011）、IS（OR = 1.007，95%CI = 1.001-1.014，p = 0.022）和心源性脑栓塞（CES）（OR = 1.018，95%CI = 1.006-1.031，p = 0.004）有积极影响。敏感性分析的点估计值方向相同。反向 MR 分析未发现 CVD 对视网膜血管阻塞影响的显著证据。
我们的 MR 研究提供了潜在的证据，表明视网膜血管阻塞与 CVD 风险增加（包括 IS、MI、中风和 CES）之间存在因果关系。这支持在有视网膜血管阻塞的个体中进行临床 CVD 筛查的必要性。需要进一步的研究来阐明 CVD 对眼部合并症的影响。
