| Title: | Polygenic basis and biomedical consequences of telomere length variation |
| Journal: | Nature Genetics |
| Published: | 5 Oct 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34611362/ |
| DOI: | https://doi.org/10.1038/s41588-021-00944-6 |
| URL: | https://www.nature.com/articles/s41588-021-00944-6.pdf |
| Citations: | 193 (135 in last 2 years) as of 8 Aug 2024 |
Publication 5562
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Abstract
Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.</p>
28 Authors
- Veryan Codd
- Qingning Wang
- Elias Allara
- Crispin Musicha
- Stephen Kaptoge
- Svetlana Stoma
- Tao Jiang
- Stephen E. Hamby
- Peter S. Braund
- Vasiliki Bountziouka
- Charley A. Budgeon
- Matthew Denniff
- Chloe Swinfield
- Manolo Papakonstantinou
- Shilpi Sheth
- Dominika E. Nanus
- Sophie C. Warner
- Minxian Wang
- Amit V. Khera
- James Eales
- Willem H. Ouwehand
- John R. Thompson
- Emanuele Di Angelantonio
- Angela M. Wood
- Adam S. Butterworth
- John N. Danesh
- Christopher P. Nelson
- Nilesh J. Samani
Enabling scientific discoveries that improve human health