Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Department of Ophthalmology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, China.
Sci Rep. 2024 Oct 23;14(1):24972. doi: 10.1038/s41598-024-76151-0.
Clinical studies and meta-analyses have suggested a link between thyroid dysfunction and lens opacification. The objective of this study is to investigate the causal relationship between hyperthyroidism and the development of cataracts using the Mendelian randomization approach, with the aim of filling the gap in knowledge about the systemic effects of hyperthyroidism on ocular health. Leveraging genetic variants as instrumental variables, the analysis used extensive datasets from the UK Biobank and the FinnGen Database and employed three common approaches for causal inference (the Inverse Variance Weighted method, a regression based method the Weighted Median estimator, and MR-Egger regression) and accompanying sensitivity analyses to ensure robustness. The results demonstrate that there is a strong likely causal relationship, with hyperthyroidism increasing the risk of developing senile cataracts (OR = 361.09, 95%CI 5.024 to 2.60 × 10, P = 0.007). A sensitivity analysis provided no evidence of horizontal pleiotropy and no significant outliers, suggesting the results are robust. In conclusion, our study established a significant causal relationship between hyperthyroidism and increased risk of cataract development, underscoring the importance of considering the systemic effects of hyperthyroidism in clinical and public health interventions and policies. Future research should focus on elucidating the molecular mechanisms underlying this association, exploring the potential benefits of early intervention in hyperthyroidism to prevent cataract development, and investigating whether these findings translate across different ethnic populations. Additionally, further GWAS studies aimed at identifying genetic variants associated with both hyperthyroidism and cataracts are warranted to confirm and expand upon our results.
临床研究和荟萃分析表明甲状腺功能障碍与晶状体混浊之间存在关联。本研究旨在通过孟德尔随机化方法探讨甲状腺功能亢进与白内障发展之间的因果关系,旨在填补关于甲状腺功能亢进对眼部健康的系统影响的知识空白。利用遗传变异作为工具变量,该分析利用了来自英国生物库和芬兰基因数据库的广泛数据集,并采用了三种常见的因果推理方法(反向方差加权法、基于回归的加权中位数估计法和 MR-Egger 回归)以及伴随的敏感性分析来确保稳健性。结果表明,存在强烈的可能因果关系,甲状腺功能亢进会增加老年性白内障的发病风险(OR=361.09,95%CI 5.024 至 2.60×10,P=0.007)。敏感性分析未提供水平多效性的证据,也没有显著的异常值,表明结果是稳健的。总之,本研究确立了甲状腺功能亢进与白内障发生风险增加之间的显著因果关系,强调了在临床和公共卫生干预措施和政策中考虑甲状腺功能亢进的系统影响的重要性。未来的研究应集中阐明这种关联的分子机制,探索早期干预甲状腺功能亢进以预防白内障发展的潜在益处,并研究这些发现是否适用于不同的种族群体。此外,需要进一步的全基因组关联研究,旨在确定与甲状腺功能亢进和白内障相关的遗传变异,以证实和扩展我们的结果。