Author Identifier
Hao Wang
Orcid: 0000-0002-9131-0199
Wei Wang
ORCID : 0000-0002-1430-1360
Xingang Li
ORCID: 0000-0003-0252-154X
Document Type
Journal Article
Publication Title
Cells
PubMed ID
30846688
Publisher
MDPI
School
School of Medical and Health Sciences
RAS ID
28589
Grant Number
NHMRC Number : 1112769
Abstract
Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from the MEGASTROKE collaboration with 40,585 stroke cases and 406,111 controls. The weighted median (WM), the penalized weighted median (PWM), the inverse variance weighted (IVW), the penalized inverse variance weighted (PIVW), the robust inverse variance weighted (RIVW), and the Mendelian randomization-Egger (MR-Egger) methods were conducted for the MR analysis to estimate a causal effect and detect the directional pleiotropy. Results: No significant association between genetically determined TL with overall IS, LAS, or CES were found (all p > 0.05). SVS was associated with TL by the RIVW method (odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.54–0.97, p = 0.028), after excluding rs9420907, rs10936599, and rs2736100. Conclusions: By a series of causal inference approaches using SNPs as IVs, no strong evidence to support the causal effect of shorter TL on IS and its subtypes were found.
DOI
10.3390/cells8020159
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Cao, W., Li, X., Zhang, X., Zhang, J., Sun, Q., Xu, X., ... & Liu, J. (2019). No causal effect of telomere length on ischemic stroke and its subtypes: A Mendelian randomization study. Cells, 8(2), 159. Available here.