| Title: | Identifying Potential Causal Effects of Telomere Length on Health Outcomes: A Phenome-Wide Investigation and Mendelian Randomization Study |
| Journal: | The Journals of Gerontology Series A |
| Published: | 20 May 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37209418/ |
| DOI: | https://doi.org/10.1093/gerona/glad128 |
| Citations: | 2 (2 in last 2 years) as of 8 Aug 2024 |
Publication 7824
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Abstract
BACKGROUND: Telomere length has been linked to various health outcomes. To comprehensively investigate the causal effects of telomere length throughout the human disease spectrum, we conducted a phenome-wide Mendelian randomization study (MR-PheWAS) and a systematic review of MR studies.</p>
METHODS: We conducted a PheWAS to screen for associations between telomere length and 1 035 phenotypes in the UK Biobank (n = 408 354). The exposure of interest was the genetic risk score (GRS) of telomere length. Observed associations passing multiple testing corrections were assessed for causality by 2-sample MR analysis. A systematic review of MR studies on telomere length was performed to harmonize the published evidence and complement our findings.</p>
RESULTS: Of the 1 035 phenotypes tested, PheWAS identified 29 and 78 associations of telomere length GRS at a Bonferroni- and false discovery rate-corrected threshold; 24 and 66 distinct health outcomes were causal in the following principal MR analysis. The replication MR using data from the FinnGen study provided evidence of causal effects of genetically instrumented telomere length on 28 out of 66 outcomes, including decreased risks of 5 diseases in respiratory diseases, digestive diseases, and myocardial infarction, and increased risks of 23 diseases, mainly comprised neoplasms, diseases of the genitourinary system, and essential hypertension. A systematic review of 53 MR studies found evidence to support 16 out of the 66 outcomes.</p>
CONCLUSIONS: This large-scale MR-PheWAS identified a wide range of health outcomes that were possibly affected by telomere length, and suggested that susceptibility to telomere length may vary across disease categories.</p>
12 Authors
- Wenxiu Wang
- Ninghao Huang
- Zhenhuang Zhuang
- Zimin Song
- Yueying Li
- Xue Dong
- Wendi Xiao
- Yimin Zhao
- Jinzhu Jia
- Zhonghua Liu
- Lu Qi
- Tao Huang
1 Application
| Application ID | Title |
|---|---|
| 44430 | Genetic risk, environmental factors and chronic diseases and ageing outcomes |
Enabling scientific discoveries that improve human health