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Telomere length and brain imaging phenotypes in UK Biobank.pdf (1.48 MB)

Telomere length and brain imaging phenotypes in UK Biobank

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posted on 2023-05-25, 09:47 authored by A Topiwala, TE Nichols, LZJ Williams, EC Robinson, F Alfaro-Almagro, B Taschler, C Wang, CP Nelson, KL Miller, V Codd, NJ Samani, SM Smith
Telomeres form protective caps at the ends of chromosomes, and their attrition is a marker of biological aging. Short telomeres are associated with an increased risk of neurological and psychiatric disorders including dementia. The mechanism underlying this risk is unclear, and may involve brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized. Here we show that leucocyte telomere length (LTL) is associated with multi-modal MRI phenotypes in 31,661 UK Biobank participants. Longer LTL is associated with: i) larger global and subcortical grey matter volumes including the hippocampus, ii) lower T1-weighted grey-white tissue contrast in sensory cortices, iii) white-matter microstructure measures in corpus callosum and association fibres, iv) lower volume of white matter hyperintensities, and v) lower basal ganglia iron. Longer LTL was protective against certain related clinical manifestations, namely all-cause dementia (HR 0.93, 95% CI: 0.91–0.96), but not stroke or Parkinson’s disease. LTL is associated with multiple MRI endophenotypes of neurodegenerative disease, suggesting a pathway by which longer LTL may confer protective against dementia.

Funding

Alcohol consumption and brain health

Wellcome Trust

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China Scholarship Council (CSC, https://www.chinesescholarshipcouncil.com/).

Integrative imaging of brain structure and function in populations and individuals

Wellcome Trust

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Linking MRI and microscopy for multi-scale neuroscience: Mechanisms, diagnostics and anatomy

Wellcome Trust

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Li Ka Shing Centre for Health Information and Discovery, an NIH grant (https://www.nih.gov/, TN: R01EB026859), the National Institute for Health Research Oxford Biomedical Research Centre (BRC-1215-20014), and a Wellcome Trust award (TEN: 100309/Z/12/Z)

Telomere length measurement in UK Biobank: advancing understanding of biological ageing and age-related diseases

Medical Research Council

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National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Centre (BRC-1215-20010)

History

Author affiliation

Department of Cardiovascular Sciences, University of Leicester

Version

  • VoR (Version of Record)

Published in

PLoS ONE

Volume

18

Issue

3 March

Pagination

e0282363

Publisher

Public Library of Science

issn

1932-6203

eissn

1932-6203

Copyright date

2023

Available date

2023-05-25

Editors

Yap P-T

Spatial coverage

United States

Language

eng

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