Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis

Abstract

Background Many contradictory conclusions pertaining to the telomere length in peripheral leukocyte chromosomes as a potential biomarker for ischemic stroke (IS) risk have been reported by the various observational studies in previous years. This study aims to investigate whether the leukocyte telomere length is associated with an increased IS risk or not, based on the Mendelian randomization (MR) approach. Methods Based on the NHGRI-EBI GWAS Catalog database, the Chinese online genetic database as well as the previous published studies, twelve single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05 were selected and the leukocyte telomere length was measured in 431 first-ever IS patients and 304 healthy controls (quantitative polymerase chain reaction). To explore linear and non-linear effect of telomere length on the IS risk, we preformed the linear MR analysis (the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method), and the non-linear MR analysis (semiparametric method with three tests for non-linearity, including the quadratic test, Cochran’s Q test, and the fractional polynomial test). Results Two verified SNPs (rs11125529 and rs412658) were chosen as instrumental variables. In linear MR analysis, the adjusted odds ratios and 95% confidence intervals of IS for genetically predicted telomere lengths, based on the two SNPs, were 1.312 (0.979 to 1.759), 1.326 (0.932 to 1.888) and 1.226 (0.844 to 1.781) for the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method, respectively. Three tests for nonlinearity failed to reject the null exactly, indicating that the relationship between telomere length and IS risk is unlikely to be non-linear. Conclusion This MR study based on individual data does not provide strong evidence for a positive linear or non-linear effect of telomere length on the IS risk.

[Retracted] Mendelian Randomization Study of Causal Relationship between Omega‐3 Fatty Acids and Risk of Lung Cancer

“…The MR-Egger method is greatly affected by the inside hypothesis [ 30 ]. When the inside hypothesis is satisfied, the type I error rate of the causal effect estimation and the bias of the gene pleiotropy effect can be well controlled; once the inside hypothesis is violated, its test performance greatly affects [ 31 ]. For the weighted median method, when the inside assumption is violated, if there are not too many invalid instrumental variables, its performance is better than the other two methods [ 32 ].…”

Leukocyte Telomere Length as a Molecular Biomarker of Coronary Heart Disease

“…This is due to the fact that the mechanisms of LTL shortening in adults, which lead to stable CAD, acute coronary syndrome (ACS), and acute myocardial infarction (AMI), have not yet been sufficiently studied [ 21 ]. LTL is also actively studied in other CVDs (essential arterial hypertension [ 22 , 23 ], atrial fibrillation [ 24 , 25 , 26 , 27 ], cardiomyopathy [ 28 ], cerebrovascular diseases (stroke [ 29 , 30 , 31 , 32 , 33 ], vascular cognitive disorders [ 34 , 35 ], and vascular dementia [ 36 ]).…”

Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study

“…[3][4][5] In addition, whether some novel factors, such as suboptimal health status and telomere length in peripheral blood leucocytes, could increase the risk of atherosclerotic cardiovascular disease (ASCVD) is being investigated. [6][7][8] Studies show that immune inflammation exerts a significant role in atherogenesis. 9 Animal experiments indicate that the initiation, growth, differentiation and rupture of atherosclerotic plaques are influenced by the immune system.…”