학술논문
Polygenic basis and biomedical consequences of telomere length variation
Document Type
Report
Author
Codd, Veryan; Wang, Qingning; Allara, Elias; Musicha, Crispin; Kaptoge, Stephen; Stoma, Svetlana; Jiang, Tao; Hamby, Stephen E.; Braund, Peter S.; Bountziouka, Vasiliki; Budgeon, Charley A.; Denniff, Matthew; Swinfield, Chloe; Papakonstantinou, Manolo; Shethm Shilpi; Nanus, Dominika E.; Warner, Sophie C.
Source
Nature Genetics. October 2021, Vol. 53 Issue 10, p1425, 9 p.
Subject
Language
English
ISSN
1061-4036
Abstract
Author(s): Veryan Codd [sup.1] [sup.2] , Qingning Wang [sup.1] [sup.2] , Elias Allara [sup.3] [sup.4] , Crispin Musicha [sup.1] [sup.2] , Stephen Kaptoge [sup.3] [sup.4] [sup.5] , Svetlana Stoma [sup.1] [...]
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 [greater than or equal to]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. Genome-wide association and Mendelian randomization analyses in the UK Biobank identify genetic variants associated with leukocyte telomere length and highlight putative causal links between telomere length and biomedical phenotypes.
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 [greater than or equal to]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. Genome-wide association and Mendelian randomization analyses in the UK Biobank identify genetic variants associated with leukocyte telomere length and highlight putative causal links between telomere length and biomedical phenotypes.