Clinical Epigenetics (Feb 2023)

Distinct DNA methylation signatures associated with blood lipids as exposures or outcomes among survivors of childhood cancer: a report from the St. Jude lifetime cohort

  • Qian Dong,
  • Cheng Chen,
  • Nan Song,
  • Na Qin,
  • Noel-Marie Plonski,
  • Emily R. Finch,
  • Kyla Shelton,
  • John Easton,
  • Heather Mulder,
  • Emily Plyer,
  • Geoffrey Neale,
  • Emily Walker,
  • Qian Li,
  • I-Chan Huang,
  • Jinghui Zhang,
  • Hui Wang,
  • Melissa M. Hudson,
  • Leslie L. Robison,
  • Kirsten K. Ness,
  • Zhaoming Wang

DOI
https://doi.org/10.1186/s13148-023-01447-3
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 14

Abstract

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Abstract Background DNA methylation (DNAm) plays an important role in lipid metabolism, however, no epigenome-wide association study (EWAS) of lipid levels has been conducted among childhood cancer survivors. Here, we performed EWAS analysis with longitudinally collected blood lipid data from survivors in the St. Jude lifetime cohort study. Methods Among 2052 childhood cancer survivors of European ancestry (EA) and 370 survivors of African ancestry (AA), four types of blood lipids, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG), were measured during follow-up beyond 5-years from childhood cancer diagnosis. For the exposure EWAS (i.e., lipids measured before blood draw for DNAm), the DNAm level was an outcome variable and each of the blood lipid level was an exposure variable; vice versa for the outcome EWAS (i.e., lipids measured after blood draw for DNAm). Results Among EA survivors, we identified 43 lipid-associated CpGs in the HDL (n = 7), TC (n = 3), and TG (n = 33) exposure EWAS, and 106 lipid-associated CpGs in the HDL (n = 5), LDL (n = 3), TC (n = 4), and TG (n = 94) outcome EWAS. Among AA survivors, we identified 15 lipid-associated CpGs in TG exposure (n = 6), HDL (n = 1), LDL (n = 1), TG (n = 5) and TC (n = 2) outcome EWAS with epigenome-wide significance (P 70%) between EA and AA survivors, highlighting differences in DNAm markers of blood lipids between populations with diverse genetic ancestry. Ten lipid-associated CpGs were cis-expression quantitative trait methylation with their DNAm levels associated with the expression of corresponding genes, out of which seven were negatively associated. Conclusions We identified distinct signatures of DNAm for blood lipids as exposures or outcomes and between EA and AA survivors, revealing additional genes involved in lipid metabolism and potential novel targets for controlling blood lipids in childhood cancer survivors.

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