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

Autor: Weijie Cao, Deqiang Zheng, Jie Zhang, Anxin Wang, Di Liu, Jinxia Zhang, Manjot Singh, Isinta Elijah Maranga, Mingyang Cao, Lijuan Wu, Manshu Song, Wei Wang, Youxin Wang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-10 (2020)
Druh dokumentu: article
ISSN: 1479-5876
DOI: 10.1186/s12967-020-02551-1
Popis: 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.
Databáze: Directory of Open Access Journals
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