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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Psychiatry | doi: 10.3389/fpsyt.2019.00843

Exploring the Causal Pathway From Telomere Length to Alzheimer’s Disease: An update Mendelian Randomization Study

Kai Gao1,  Xin Wang2, Jin Zhu2, Yangyang Luo2, Guoqing Chen2, Dai Zhang3,  Weihua Yue3 and  Hao Yu2*
  • 1Peking-Tsinghua Center for Life Sciences, China
  • 2Jining Medical University, China
  • 3Key Laboratory of Mental Health, Ministry of Health, Peking University, China

Increasing evidence shows that telomere length shortening is associated with the risk for Alzheimer’s disease (AD), pointing to a potential modifiable target for prevention. However, the causality of this association is still not clear. To investigate the causal relationship between telomere length and AD, we use two-sample Mendelian randomization (MR) to assessing potential causal inference. We used summary-level data for telomere length (9190 participants) and AD (71,880 cases and 383,378 controls). We performed two-sample MR analysis with single nucleotide polymorphisms previously identified to be associated with telomere length. The MR analyses were conducted using the inverse-variance-weighted method and complemented with the maximum likelihood, weighted median, weighted mode approaches. MR evidence suggested that shorter telomere length was causally associated with a higher risk for AD (IVW estimate of odds ratio (OR): 1.03 per SD decrease of telomere length, P=1.21×10-2). The maximum likelihood, weighted median, weighted mode yielded a similar pattern of effects. The results were similar in sensitivity analyses. Using genetic instruments identified from large-scale GWAS, robust evidence supports a causal role of telomere length shortening with increased risk of AD.

Keywords: telomere length, Alzheimer's disease, genome-wide association study (GWAS), Genetic instrument, Mendelian randomization

Received: 26 Aug 2019; Accepted: 24 Oct 2019.

Copyright: © 2019 Gao, Wang, Zhu, Luo, Chen, Zhang, Yue and Yu. 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) and the copyright owner(s) 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: Dr. Hao Yu, Jining Medical University, Jining, Shandong, China, yuhao@mail.jnmc.edu.cn