Polygenic basis and biomedical consequences of telomere length variation.
View / Open Files
Authors
Codd, Veryan
Wang, Qingning
Musicha, Crispin
Stoma, Svetlana
Jiang, Tao
Hamby, Stephen E
Braund, Peter S
Bountziouka, Vasiliki
Budgeon, Charley A
Denniff, Matthew
Swinfield, Chloe
Papakonstantinou, Manolo
Sheth, Shilpi
Nanus, Dominika E
Warner, Sophie C
Wang, Minxian
Khera, Amit V
Eales, James
Ouwehand, Willem H
Thompson, John R
Wood, Angela M
Butterworth, Adam S
Danesh, John N
Nelson, Christopher P
Samani, Nilesh J
Publication Date
2021-10Journal Title
Nature Genetics
ISSN
1061-4036
Publisher
Nature Research
Volume
53
Issue
10
Pages
1425-1433
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Codd, V., Wang, Q., Allara, E., Musicha, C., Kaptoge, S., Stoma, S., Jiang, T., et al. (2021). Polygenic basis and biomedical consequences of telomere length variation.. Nature Genetics, 53 (10), 1425-1433. https://doi.org/10.1038/s41588-021-00944-6
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.
Sponsorship
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
British Heart Foundation (CH/12/2/29428)
Medical Research Council (MR/M012816/1)
British Heart Foundation (RG/18/13/33946)
National Institute for Health Research (IS-BRC-1215-20014)
Identifiers
External DOI: https://doi.org/10.1038/s41588-021-00944-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330378
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.