Association between genetically determined telomere length and health-related outcomes: A systematic review and meta-analysis of Mendelian randomization studies.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of Mendelian randomization studies (analogous to systematic review of natural experiments)
PubMed 37232505 · doi:10.1111/acel.13874
What was done
A systematic review and meta-analysis of Mendelian randomization (MR) studies was conducted to assess causal associations between leukocyte telomere length (LTL) and health-related outcomes. Literature was searched across PubMed, Embase, and Web of Science up to April 2022. Evidence was graded across primary analyses and four sensitivity methods (MR-Egger, weighted median, MR-PRESSO, and multivariable MR), alongside pooled meta-analyses of published MR studies.
What was found
The review included 62 studies covering 310 outcomes and 396 MR associations. Genetically longer LTL showed robust associations with increased risk of 24 neoplasms (strongest magnitude for osteosarcoma, glioblastoma, glioma, thyroid cancer, and non-GBM glioma), six genitourinary/digestive conditions involving abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse associations (protective effects) were observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses identified associations with 12 neoplasms and 9 nonneoplasm outcomes. Exact numerical effect sizes and confidence intervals were not reported in the abstract.
Why it matters
This synthesis demonstrates an evolutionary trade-off where genetically longer telomeres increase the risk of diverse cancers and hyperproliferative conditions while protecting against cardiovascular, fibrotic, and degenerative diseases.
Limits
The abstract does not provide specific numerical effect estimates or confidence intervals. Findings depend on standard Mendelian randomization assumptions (such as lack of horizontal pleiotropy), and participant characteristics or ancestry were not detailed in the abstract.
Cited by
- supports Mendelian randomization studies show that genetic propensity for longer telomeres directly predicts reduced risk of heart disease and dementia.