Association between genetically determined telomere length and health‐related outcomes: A systematic review and meta‐analysis of Mendelian randomization studies

Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health‐related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta‐analysis of current evidence from Mendelian randomization (MR) studies on the asso...

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Bibliographic Details
Published in:Aging cell 2023-07, Vol.22 (7), p.e13874-n/a
Main Authors: Chen, Boran, Yan, Yushun, Wang, Haoran, Xu, Jianguo
Format: Article
Language:English
Subjects:
Arthritis, Rheumatoid
Coronary artery disease
Fibrosis
Genome-Wide Association Study
Glioma
health‐related outcomes
Heart diseases
Hemopoiesis
Humans
Hypertension
Kidney diseases
leukocyte telomere length
Leukocytes
Lung diseases
Mendelian randomization
Mendelian Randomization Analysis - methods
Meta-analysis
Metabolic syndrome
Multiple sclerosis
Observational studies
Osteosarcoma
Polymorphism, Single Nucleotide
Review
Rheumatoid arthritis
Statistical significance
Systematic review
Telomerase
Telomere - genetics
Telomeres
Therapeutic applications
Thyroid cancer
Variables
Yeast
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Summary:Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health‐related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta‐analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health‐related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR‐Egger, weighted median, MR‐PRESSO, and multivariate MR. Meta‐analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non‐GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta‐analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length. This systematic review and meta‐analysis found that genetically determined telomere length was robustly associated with increased risk of neoplasms, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential and decreased risk of coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging.
ISSN:1474-9718
1474-9726
DOI:10.1111/acel.13874