Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese populati
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Journal of Translational Medicine Open Access
RESEARCH
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 Weijie Cao1†, Deqiang Zheng1†, Jie Zhang1, Anxin Wang2,3, Di Liu1, Jinxia Zhang1, Manjot Singh4, Isinta Elijah Maranga1, Mingyang Cao1, Lijuan Wu1, Manshu Song4, Wei Wang1,4* and Youxin Wang1,4*
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 nonlinearity, 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 nonlinear effect of telomere length on the IS risk.
*Correspondence: [email protected]; [email protected] † Weijie Cao and Deqiang Zheng contributed equally to this work 1 Department of Epidemiology and Health Statistics, School of Public Health, Beijing Key Laboratory of Clinical Epidemiology, Capital Medical University, No. 10 Xitoutiao, Youanmen, Fengtai District, Beijing 100069, China Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original
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