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Investigating the impact of metabolic syndrome traits on telomere length: a Mendelian randomization study

Abstract:
Objective
Observational studies have reported bidirectional associations between metabolic syndrome (MetS) traits and short leukocyte telomere length (LTL), a TL marker in somatic tissues and a proposed risk factor for age-related degenerative diseases. However, in Mendelian randomization studies, longer LTL has been paradoxically associated with higher MetS risk. This study investigated the hypothesis that shorter LTL might be a consequence of metabolic dysfunction.
Methods
This study undertook univariable and multivariable Mendelian randomization. As instrumental variables for MetS traits, all of the genome-wide significant independent signals identified in genome-wide association studies for anthropometric, glycemic, lipid, and blood pressure traits conducted in European individuals were used. Summary-level data for LTL were obtained from a genome-wide association study conducted in the UK Biobank.
Results
Higher BMI was associated with shorter LTL (β = −0.039, 95% CI: −0.058 to −0.020, p = 5 × 10−5) equivalent to 1.70 years of age-related LTL change. In contrast, higher low-density lipoprotein cholesterol was associated with longer LTL (β = 0.022, 95% CI: 0.007 to 0.037, p = 0.003) equivalent to 0.96 years of age-related LTL change. Mechanistically, increased low-grade systemic inflammation, as measured by circulating C-reactive protein, and lower circulating linoleic acid levels might link higher BMI to shorter LTL.
Conclusions
Overweight and obesity might promote the development of aging-related degenerative diseases by accelerating telomere shortening.
Publication status:
Published
Peer review status:
Peer reviewed

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Files:
Publisher copy:
10.1002/oby.23810

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
OCDEM
Oxford college:
Wolfson College
Role:
Author
ORCID:
0000-0001-5154-0785


Publisher:
Wiley
Journal:
Obesity More from this journal
Volume:
31
Issue:
8
Pages:
2189-2198
Publication date:
2023-07-06
Acceptance date:
2023-04-26
DOI:
EISSN:
1930-739X
ISSN:
1930-7381


Language:
English
Keywords:
Pubs id:
1337755
Local pid:
pubs:1337755
Deposit date:
2023-04-19

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