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Telomere length is causally connected to brain MRI image derived phenotypes: A mendelian randomization study

Salih, Ahmed; Galazzo, Ilaria Boscolo; Petersen, Steffen E; Lekadir, Karim; Radeva, Petia; Menegaz, Gloria; Altmann, André; (2022) Telomere length is causally connected to brain MRI image derived phenotypes: A mendelian randomization study. PLOS ONE , 17 (11) , Article e0277344. 10.1371/journal.pone.0277344. Green open access

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Abstract

Recent evidence suggests that shorter telomere length (TL) is associated with neuro degenerative diseases and aging related outcomes. The causal association between TL and brain characteristics represented by image derived phenotypes (IDPs) from different magnetic resonance imaging (MRI) modalities remains unclear. Here, we use two-sample Mendelian randomization (MR) to systematically assess the causal relationships between TL and 3,935 brain IDPs. Overall, the MR results suggested that TL was causally associated with 193 IDPs with majority representing diffusion metrics in white matter tracts. 68 IDPs were negatively associated with TL indicating that longer TL causes decreasing in these IDPs, while the other 125 were associated positively (longer TL leads to increased IDPs measures). Among them, ten IDPs have been previously reported as informative biomarkers to estimate brain age. However, the effect direction between TL and IDPs did not reflect the observed direction between aging and IDPs: longer TL was associated with decreases in fractional anisotropy and increases in axial, radial and mean diffusivity. For instance, TL was positively associated with radial diffusivity in the left perihippocampal cingulum tract and with mean diffusivity in right perihippocampal cingulum tract. Our results revealed a causal role of TL on white matter integrity which makes it a valuable factor to be considered when brain age is estimated and investigated.

Type: Article
Title: Telomere length is causally connected to brain MRI image derived phenotypes: A mendelian randomization study
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0277344
Publisher version: https://doi.org/10.1371/journal.pone.0277344
Language: English
Additional information: Copyright © 2022 Salih et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Telomere length, Genome-wide association studies, Single nucleotide polymorphisms, Central nervous system, Magnetic resonance imaging, Telomeres, Alzheimer's disease, Genomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10160159
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