期刊
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1111/eci.14056
关键词
aortic aneurysm; genome-wide association study; instrumental variable; Mendelian randomisation; single-nucleotide polymorphism; telomere length
This study used a Mendelian randomisation approach to investigate the causal relationship between telomere length and aortic aneurysms. The results showed that longer telomere length can decrease the risk of aortic aneurysms, providing new insights into the potential causal association between them.
Background: Evidence of a clear causal relationship between telomere length and aortic aneurysms is limited by the potential for confounding or reverse causation effects. In this study, we used a Mendelian randomisation (MR) approach to investigate this putative causal association. Methods: In total, 118 telomere length-associated single-nucleotide polymorphisms, identified in 472,174 individuals of European ancestry, were used as the instrumental variables. Summary statistics for genome-wide association studies of aortic aneurysms were obtained from the FinnGen consortium. For the primary MR analyses, the inverse-variance weighted random-effects method was used and was supplemented with multivariable MR, weighted median and MR-Egger approaches. The MR-Egger intercept test, Cochran's Q test and 'leave-one-out' sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneity and stability of the genetic variants. Forward and reverse MR analyses were performed. Results: All forward univariable MR analyses showed that longer telomere lengths decreased aortic aneurysm risks (total aortic aneurysms: OR = 0.80, 95% CI 0.67-0.96, p =.015; thoracic aortic aneurysms: OR = 0.82, 95% CI 0.68-0.98, p =.026; abdominal aortic aneurysms: OR = 0.525, 95% CI 0.398-0.69, p <.001), whereas all reverse MR analyses suggested the absence of aortic aneurysm liability on telomere length. The sensitivity analysis results were robust, and no evidence of horizontal pleiotropy was observed. Conclusions: Our results support a possible causal association between telomere length and aortic aneurysms, providing new insights into the involvement of telomere biology in this condition and offering a potential avenue for targeted therapeutic interventions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据