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Polygenic basis and biomedical consequences of telomere length variation
- Source :
- Codd, V, Wang, Q, Allara, E, Musicha, C, Kaptoge, S, Stoma, S, Jiang, T, Hamby, S E, Braund, P S, Bountziouka, V, Budgeon, C A, Denniff, M, Swinfield, C, Papakonstantinou, M, Sheth, S, Nanus, D E, Warner, S C, Wang, M, Khera, A V, Eales, J, Ouwehand, W H, Di Angelantonio, E, Wood, A M, Butterworth, A S, Danesh, J N & Samani, N J 2021, ' Polygenic basis and biomedical consequences of telomere length variation ', Nature Genetics, vol. 53, no. 10, pp. 1425-1433 . https://doi.org/10.1038/s41588-021-00944-6, Nature Genetics
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group US, 2021.
-
Abstract
- Funder: Health Data Research UK EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart (11607).<br />Funder: Health Data Research UK<br />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.
- Subjects :
- Senescence
Multifactorial Inheritance
media_common.quotation_subject
Quantitative Trait Loci
631/208/205/2138
45/43
Computational biology
Biology
Genome-wide association studies
Health data
Length variation
Genetics research
Genetics
Humans
media_common
Basis (linear algebra)
Genome, Human
Longevity
692/308/2056
article
Telomere Homeostasis
Mendelian Randomization Analysis
Biobank
Phenotype
Genetic architecture
Telomere
Evolutionary biology
Function (biology)
Genome-Wide Association Study
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Codd, V, Wang, Q, Allara, E, Musicha, C, Kaptoge, S, Stoma, S, Jiang, T, Hamby, S E, Braund, P S, Bountziouka, V, Budgeon, C A, Denniff, M, Swinfield, C, Papakonstantinou, M, Sheth, S, Nanus, D E, Warner, S C, Wang, M, Khera, A V, Eales, J, Ouwehand, W H, Di Angelantonio, E, Wood, A M, Butterworth, A S, Danesh, J N & Samani, N J 2021, ' Polygenic basis and biomedical consequences of telomere length variation ', Nature Genetics, vol. 53, no. 10, pp. 1425-1433 . https://doi.org/10.1038/s41588-021-00944-6, Nature Genetics
- Accession number :
- edsair.doi.dedup.....79a5f7b77fb929a25e4a9d6bfe70b7d5