Codd, V;
Wang, Q;
Allara, E;
Musicha, C;
Kaptoge, S;
Stoma, S;
Jiang, T;
... Samani, NJ; + view all
(2021)
Polygenic basis and biomedical consequences of telomere length variation.
Nature Genetics
, 53
(10)
pp. 1425-1433.
10.1038/s41588-021-00944-6.
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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.
| Type: | Article |
|---|---|
| Title: | Polygenic basis and biomedical consequences of telomere length variation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41588-021-00944-6 |
| Publisher version: | https://doi.org/10.1038/s41588-021-00944-6 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENOME-WIDE ASSOCIATION, MENDELIAN RANDOMIZATION, CANCER, RISK, METAANALYSIS, MORTALITY, PATHWAYS, REVEALS, LINKS, RNA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10140195 |
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