Wang Guoqing, Yi Xianglong
Department of Ophthalmology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Xinjiang Medical University, Urumqi, China.
Medicine (Baltimore). 2025 Mar 14;104(11):e41794. doi: 10.1097/MD.0000000000041794.
Myopia has been extensively documented as a significant risk factor for cataracts; however, the relationship between hyperopia and cataract development remains poorly understood. Given the distinct refractive profiles of myopia and hyperopia, hyperopia may confer a protective effect against cataracts. In this study, we employed Mendelian randomization (MR) to examine the causal association between hyperopia and cataracts. A 2-sample MR framework was utilized to examine the causal relationship between hyperopia and cataracts, with multivariable MR implemented to account for potential confounding variables. The inverse variance weighted (IVW) method served as the primary analytical tool, complemented by multiple sensitivity analyses to ensure the robustness and reliability of the findings. Enrichment analyses were conducted to elucidate the underlying biological pathways, while Bayesian colocalization analysis pinpointed shared genetic loci that influence both hyperopia and cataracts. In our study, we found that hyperopia may exert a protective effect against cataracts (IVW odds ratio, 0.920 [95% confidence interval, 0.872-0.972]; P = .0029) and cataract surgery (IVW odds ratio, 0.811 [95% confidence interval, 0.754-0.873]; P < .0001). Multivariable MR, adjusting for confounding factors such as smoking, glaucoma, and diabetes, confirmed hyperopia's protective association with cataracts. Bayesian colocalization identified rs12193446 as a high-probability shared causal variant, while enrichment analyses revealed potential biological mechanisms linking hyperopia to cataract development. Genetic evidence suggests that higher levels of hyperopia are associated with a reduced risk of age-related nuclear cataracts, cataract extraction, and lens implants. Given the opposite refractive states of myopia and hyperopia and their opposite effects on cataracts, these findings provide new insights into the pathogenesis of age-related cataracts.
近视已被广泛记录为白内障的一个重要风险因素；然而，远视与白内障发展之间的关系仍知之甚少。鉴于近视和远视不同的屈光特征，远视可能对白内障具有保护作用。在本研究中，我们采用孟德尔随机化（MR）方法来检验远视与白内障之间的因果关联。利用两样本MR框架来检验远视与白内障之间的因果关系，并实施多变量MR以考虑潜在的混杂变量。逆方差加权（IVW）方法作为主要分析工具，并辅以多种敏感性分析以确保研究结果的稳健性和可靠性。进行了富集分析以阐明潜在的生物学途径，而贝叶斯共定位分析则确定了影响远视和白内障的共同基因位点。在我们的研究中，我们发现远视可能对白内障具有保护作用（IVW优势比，0.920 [95%置信区间，0.872 - 0.972]；P = 0.0029）以及对白内障手术具有保护作用（IVW优势比，0.811 [95%置信区间，0.754 - 0.873]；P < 0.0001）。调整吸烟、青光眼和糖尿病等混杂因素后的多变量MR证实了远视与白内障之间的保护性关联。贝叶斯共定位确定rs12193446为高概率的共同因果变异，而富集分析揭示了将远视与白内障发展联系起来的潜在生物学机制。遗传证据表明，较高程度的远视与年龄相关性核性白内障、白内障摘除和晶状体植入的风险降低相关。鉴于近视和远视相反的屈光状态及其对白内障的相反影响，这些发现为年龄相关性白内障的发病机制提供了新的见解。
