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Clonal hematopoiesis associated with epigenetic aging and clinical outcomes.

Publication ,  Journal Article
Nachun, D; Lu, AT; Bick, AG; Natarajan, P; Weinstock, J; Szeto, MD; Kathiresan, S; Abecasis, G; Taylor, KD; Guo, X; Tracy, R; Durda, P ...
Published in: Aging Cell
June 2021

Clonal hematopoiesis of indeterminate potential (CHIP) is a common precursor state for blood cancers that most frequently occurs due to mutations in the DNA-methylation modifying enzymes DNMT3A or TET2. We used DNA-methylation array and whole-genome sequencing data from four cohorts together comprising 5522 persons to study the association between CHIP, epigenetic clocks, and health outcomes. CHIP was strongly associated with epigenetic age acceleration, defined as the residual after regressing epigenetic clock age on chronological age, in several clocks, ranging from 1.31 years (GrimAge, p < 8.6 × 10-7 ) to 3.08 years (EEAA, p < 3.7 × 10-18 ). Mutations in most CHIP genes except DNA-damage response genes were associated with increases in several measures of age acceleration. CHIP carriers with mutations in multiple genes had the largest increases in age acceleration and decrease in estimated telomere length. Finally, we found that ~40% of CHIP carriers had acceleration >0 in both Hannum and GrimAge (referred to as AgeAccelHG+). This group was at high risk of all-cause mortality (hazard ratio 2.90, p < 4.1 × 10-8 ) and coronary heart disease (CHD) (hazard ratio 3.24, p < 9.3 × 10-6 ) compared to those who were CHIP-/AgeAccelHG-. In contrast, the other ~60% of CHIP carriers who were AgeAccelHG- were not at increased risk of these outcomes. In summary, CHIP is strongly linked to age acceleration in multiple clocks, and the combination of CHIP and epigenetic aging may be used to identify a population at high risk for adverse outcomes and who may be a target for clinical interventions.

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Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

June 2021

Volume

20

Issue

6

Start / End Page

e13366

Location

England

Related Subject Headings

  • Treatment Outcome
  • Risk Factors
  • Humans
  • Epigenomics
  • Developmental Biology
  • Clonal Hematopoiesis
  • Aging
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
 

Citation

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Nachun, D., Lu, A. T., Bick, A. G., Natarajan, P., Weinstock, J., Szeto, M. D., … NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, . (2021). Clonal hematopoiesis associated with epigenetic aging and clinical outcomes. Aging Cell, 20(6), e13366. https://doi.org/10.1111/acel.13366
Nachun, Daniel, Ake T. Lu, Alexander G. Bick, Pradeep Natarajan, Joshua Weinstock, Mindy D. Szeto, Sekar Kathiresan, et al. “Clonal hematopoiesis associated with epigenetic aging and clinical outcomes.Aging Cell 20, no. 6 (June 2021): e13366. https://doi.org/10.1111/acel.13366.
Nachun D, Lu AT, Bick AG, Natarajan P, Weinstock J, Szeto MD, et al. Clonal hematopoiesis associated with epigenetic aging and clinical outcomes. Aging Cell. 2021 Jun;20(6):e13366.
Nachun, Daniel, et al. “Clonal hematopoiesis associated with epigenetic aging and clinical outcomes.Aging Cell, vol. 20, no. 6, June 2021, p. e13366. Pubmed, doi:10.1111/acel.13366.
Nachun D, Lu AT, Bick AG, Natarajan P, Weinstock J, Szeto MD, Kathiresan S, Abecasis G, Taylor KD, Guo X, Tracy R, Durda P, Liu Y, Johnson C, Rich SS, Van Den Berg D, Laurie C, Blackwell T, Papanicolaou GJ, Correa A, Raffield LM, Johnson AD, Murabito J, Manson JE, Desai P, Kooperberg C, Assimes TL, Levy D, Rotter JI, Reiner AP, Whitsel EA, Wilson JG, Horvath S, Jaiswal S, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium. Clonal hematopoiesis associated with epigenetic aging and clinical outcomes. Aging Cell. 2021 Jun;20(6):e13366.
Journal cover image

Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

June 2021

Volume

20

Issue

6

Start / End Page

e13366

Location

England

Related Subject Headings

  • Treatment Outcome
  • Risk Factors
  • Humans
  • Epigenomics
  • Developmental Biology
  • Clonal Hematopoiesis
  • Aging
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences