Epigenome-wide association study of leukocyte telomere length

Yunsung Lee, Dianjianyi Sun, Anil P.S. Ori, Ake T. Lu, Anne Seeboth, Sarah E. Harris, Ian J. Deary, Riccardo E. Marioni, Mette Soerensen, Jonas Mengel-From, Jacob Hjelmborg, Kaare Christensen, James G. Wilson, Daniel Levy, Alex P. Reiner, Wei Chen, Shengxu Li, Jennifer R. Harris, Per Magnus, Abraham AvivAstanand Jugessur, Steve Horvath

Research output: Contribution to journalArticle

Abstract

Telomere length is associated with age-related diseases and is highly heritable. It is unclear, however, to what extent epigenetic modifications are associated with leukocyte telomere length (LTL). In this study, we conducted a large-scale epigenome-wide association study (EWAS) of LTL using seven large cohorts (n=5,713) - the Framingham Heart Study, the Jackson Heart Study, the Women's Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins. Our stratified analysis suggests that EWAS findings for women of African ancestry may be distinct from those of three other groups: males of African ancestry, and males and females of European ancestry. Using a meta-analysis framework, we identified DNA methylation (DNAm) levels at 823 CpG sites to be significantly associated (P < 1E-7) with LTL after adjusting for age, sex, ethnicity, and imputed white blood cell counts. Functional enrichment analyses revealed that these CpG sites are near genes that play a role in circadian rhythm, blood coagulation, and wound healing. Weighted correlation network analysis identified four co-methylation modules associated with LTL, age, and blood cell counts. Overall, this study reveals highly significant relationships between two hallmarks of aging: telomere biology and epigenetic changes.

Original languageEnglish (US)
Pages (from-to)5876-5894
Number of pages19
JournalAging
Volume11
Issue number16
DOIs
StatePublished - Jan 1 2019

Fingerprint

Telomere
Leukocytes
Epigenomics
Blood Cell Count
Blood Coagulation
Women's Health
DNA Methylation
Circadian Rhythm
Leukocyte Count
Wound Healing
Methylation
Longitudinal Studies
Meta-Analysis
Parturition
Genes

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

Keywords

  • DNA methylation
  • Leukocyte telomere length
  • Multi-ancestry

Cite this

Lee, Y., Sun, D., Ori, A. P. S., Lu, A. T., Seeboth, A., Harris, S. E., ... Horvath, S. (2019). Epigenome-wide association study of leukocyte telomere length. Aging, 11(16), 5876-5894. https://doi.org/10.18632/aging.102230
Lee, Yunsung ; Sun, Dianjianyi ; Ori, Anil P.S. ; Lu, Ake T. ; Seeboth, Anne ; Harris, Sarah E. ; Deary, Ian J. ; Marioni, Riccardo E. ; Soerensen, Mette ; Mengel-From, Jonas ; Hjelmborg, Jacob ; Christensen, Kaare ; Wilson, James G. ; Levy, Daniel ; Reiner, Alex P. ; Chen, Wei ; Li, Shengxu ; Harris, Jennifer R. ; Magnus, Per ; Aviv, Abraham ; Jugessur, Astanand ; Horvath, Steve. / Epigenome-wide association study of leukocyte telomere length. In: Aging. 2019 ; Vol. 11, No. 16. pp. 5876-5894.
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Lee, Y, Sun, D, Ori, APS, Lu, AT, Seeboth, A, Harris, SE, Deary, IJ, Marioni, RE, Soerensen, M, Mengel-From, J, Hjelmborg, J, Christensen, K, Wilson, JG, Levy, D, Reiner, AP, Chen, W, Li, S, Harris, JR, Magnus, P, Aviv, A, Jugessur, A & Horvath, S 2019, 'Epigenome-wide association study of leukocyte telomere length', Aging, vol. 11, no. 16, pp. 5876-5894. https://doi.org/10.18632/aging.102230

Epigenome-wide association study of leukocyte telomere length. / Lee, Yunsung; Sun, Dianjianyi; Ori, Anil P.S.; Lu, Ake T.; Seeboth, Anne; Harris, Sarah E.; Deary, Ian J.; Marioni, Riccardo E.; Soerensen, Mette; Mengel-From, Jonas; Hjelmborg, Jacob; Christensen, Kaare; Wilson, James G.; Levy, Daniel; Reiner, Alex P.; Chen, Wei; Li, Shengxu; Harris, Jennifer R.; Magnus, Per; Aviv, Abraham; Jugessur, Astanand; Horvath, Steve.

In: Aging, Vol. 11, No. 16, 01.01.2019, p. 5876-5894.

Research output: Contribution to journalArticle

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AU - Seeboth, Anne

AU - Harris, Sarah E.

AU - Deary, Ian J.

AU - Marioni, Riccardo E.

AU - Soerensen, Mette

AU - Mengel-From, Jonas

AU - Hjelmborg, Jacob

AU - Christensen, Kaare

AU - Wilson, James G.

AU - Levy, Daniel

AU - Reiner, Alex P.

AU - Chen, Wei

AU - Li, Shengxu

AU - Harris, Jennifer R.

AU - Magnus, Per

AU - Aviv, Abraham

AU - Jugessur, Astanand

AU - Horvath, Steve

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N2 - Telomere length is associated with age-related diseases and is highly heritable. It is unclear, however, to what extent epigenetic modifications are associated with leukocyte telomere length (LTL). In this study, we conducted a large-scale epigenome-wide association study (EWAS) of LTL using seven large cohorts (n=5,713) - the Framingham Heart Study, the Jackson Heart Study, the Women's Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins. Our stratified analysis suggests that EWAS findings for women of African ancestry may be distinct from those of three other groups: males of African ancestry, and males and females of European ancestry. Using a meta-analysis framework, we identified DNA methylation (DNAm) levels at 823 CpG sites to be significantly associated (P < 1E-7) with LTL after adjusting for age, sex, ethnicity, and imputed white blood cell counts. Functional enrichment analyses revealed that these CpG sites are near genes that play a role in circadian rhythm, blood coagulation, and wound healing. Weighted correlation network analysis identified four co-methylation modules associated with LTL, age, and blood cell counts. Overall, this study reveals highly significant relationships between two hallmarks of aging: telomere biology and epigenetic changes.

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Lee Y, Sun D, Ori APS, Lu AT, Seeboth A, Harris SE et al. Epigenome-wide association study of leukocyte telomere length. Aging. 2019 Jan 1;11(16):5876-5894. https://doi.org/10.18632/aging.102230