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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Neuroepidemiology
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1393825

Association between telomere length and idiopathic normal pressure hydrocephalus: a Mendelian randomization study

Provisionally accepted
Feng Yang Feng Yang 1Hanlin Cai Hanlin Cai 1Yimeng Ren Yimeng Ren 1Keru Huang Keru Huang 2Hui Gao Hui Gao 1Linyuan Qin Linyuan Qin 1Ruihan Wang Ruihan Wang 1Yongping Chen Yongping Chen 1Liangxue Zhou Liangxue Zhou 2Dong Zhou Dong Zhou 1Qin Chen Qin Chen 1*
  • 1 Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
  • 2 Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    Objective: Idiopathic normal pressure hydrocephalus (iNPH) is highly prevalent among elderly individuals, and there is a strong correlation between telomere length and biological aging. However, there is limited evidence to elucidate the relationship between telomere length and iNPH. This study aimed to investigate the associations between telomere length and iNPH using the Mendelian randomization (MR) method.The genetic variants of telomere length were obtained from 472,174 UK Biobank individuals. Summary level data of iNPH were acquired from 218,365 individuals of the FinnGen consortium. Five MR estimation methods, including inverse-variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode, were used for causal inference.Comprehensive sensitivity analyses were conducted to test the robustness of the results. In addition, multivariable MR was further implemented to identify potential mechanisms in the causal pathway from telomere length to iNPH.Results: Genetically determined longer telomere length was significantly associated with decreased risk of iNPH (OR=0.44, 95% CI 0.24-0.80; P=0.008). No evident heterogeneity (Cochran Q=138.11, P=0.386) and pleiotropy (MR Egger intercept=0.01, P=0.514) were observed in the sensitivity analysis. In addition, multivariable MR indicated that the observed association was attenuated after adjustment for several vascular risk factors, including essential hypertension (IVW OR=0.55, 95% CI 0.30-1.03; P=0.061), type 2 diabetes (IVW OR=0.71, 95% CI 0.09-5.39; P=0.740) and coronary artery disease (IVW OR=0.58, 95% CI 0.31-1.07; P=0.082).Our MR study revealed a strong negative correlation of telomere length with iNPH.The causal relationship might be driven by several vascular risk factors.

    Keywords: telomere length, idiopathic normal pressure hydrocephalus, Mendelian randomization, vascular risk factors, causal relationship telomere length, causal relationship

    Received: 02 Mar 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Yang, Cai, Ren, Huang, Gao, Qin, Wang, Chen, Zhou, Zhou and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Qin Chen, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

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