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2. Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank

Author

Codd, V, Denniff, M, Swinfield, C, Warner, SC, Papakonstantinou, M, Sheth, S, Nanus, DE, Budgeon, CA, Musicha, C, Bountziouka, V, Wang, Q, Bramley, R, Allara, E, Kaptoge, S, Stoma, S, Jiang, T, Butterworth, AS, Wood, AM, Di Angelantonio, E, Thompson, Danesh, JN, Nelson, CP, Samani, NJ, Codd, V [0000-0002-9430-8254], Papakonstantinou, M [0000-0003-2664-9046], Budgeon, CA [0000-0002-1910-5561], Allara, E [0000-0002-1634-8330], Butterworth, AS [0000-0002-6915-9015], Thompson, JR [0000-0003-4819-1611], Samani, NJ [0000-0002-3286-8133], and Apollo - University of Cambridge Repository

Subjects
Male, Aging, Neuroscience (miscellaneous), Infant, Newborn, Ethnicity, Leukocytes, Humans, Female, Geriatrics and Gerontology, Telomere, United Kingdom, Biological Specimen Banks
Abstract

Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.

Published
2022

3. A major population resource of 474,074 participants in UK Biobank to investigate determinants and biomedical consequences of leukocyte telomere length

Author

Codd, V., primary, Denniff, M., additional, Swinfield, C., additional, Warner, S.C., additional, Papakonstantinou, M., additional, Sheth, S., additional, Nanus, D.E., additional, Budgeon, C.A., additional, Musicha, C., additional, Bountziouka, V., additional, Wang, Q., additional, Bramley, R., additional, Allara, E., additional, Kaptoge, S., additional, Stoma, S., additional, Jiang, T., additional, Butterworth, A.S., additional, Wood, A.M., additional, Di Angelantonio, E., additional, Thompson, J.R., additional, Danesh, J.N., additional, Nelson, C.P., additional, and Samani, N. J., additional

Published
2021
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4. Polygenic basis and biomedical consequences of telomere length variation.

Author

Codd V, Wang Q, Allara E, Musicha C, Kaptoge S, Stoma S, Jiang T, Hamby SE, Braund PS, Bountziouka V, Budgeon CA, Denniff M, Swinfield C, Papakonstantinou M, Sheth S, Nanus DE, Warner SC, Wang M, Khera AV, Eales J, Ouwehand WH, Thompson JR, Di Angelantonio E, Wood AM, Butterworth AS, Danesh JN, Nelson CP, and Samani NJ

Subjects
Genome, Human, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Quantitative Trait Loci, Multifactorial Inheritance genetics, Telomere Homeostasis genetics
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., (© 2021. The Author(s).)

Published
2021
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