Genetic evidence for the causal linkage between telomere length and aortic aneurysm risk: A Mendelian randomisation study

Abstract

BackgroundEvidence 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.MethodsIn 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.ResultsAll 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.ConclusionsOur 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.

Causal relationship between telomere length and risk of intracranial aneurysm: a bidirectional Mendelian randomization study

“…The occurrence of aneurysms in the anterior circulation arteries after the bifurcation of the internal carotid artery, as well as ascending aortic aneurysms, may be influenced to a greater extent by genetic factors. The MR study conducted by Zhang et al ( 4 ) provides additional evidence in support of a causal association between telomere length and arterial aneurysms. Specifically, the study found that individuals with longer telomere length had a decreased chance of developing arterial aneurysms.…”

“…There may be shared genetic and pathological factors between them ( 3 ). Recent research findings suggest a potential causal association between the length of telomeres and the occurrence of aortic aneurysms ( 4 ). These findings offer promising prospects for the development of tailored treatment strategies.…”