Whole-genome differentially hydroxymethylated DNA regions among twins discordant for cardiovascular death

Jun Dai, Ming Leung, Weihua Guan, Han Tian Guo, Ruth E. Krasnow, Thomas J. Wang, Wael El-rifai, Zhongming Zhao, Terry Reed

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Epigenetics is a mechanism underlying cardiovascular disease. It is unknown whether DNA hydroxymethylation is prospectively associated with the risk for cardiovascular death independent of germline and common environment. Male twin pairs middle-aged in 1969–1973 and discordant for cardiovascular death through December 31, 2014, were included. Hydroxymethyla-tion was quantified in buffy coat DNA collected in 1986–1987. The 1893 differentially hydroxymeth-ylated regions (DhMRs) were identified after controlling for blood leukocyte subtypes and age among 12 monozygotic (MZ) pairs (Benjamini–Hochberg False Discovery Rate < 0.01), of which the 102 DhMRs were confirmed with directionally consistent log2-fold changes and p < 0.01 among ad-ditional 7 MZ pairs. These signature 102 DhMRs, independent of the germline, were located on all chromosomes except for chromosome 21 and the Y chromosome, mainly within/overlapped with intergenic regions and introns, and predominantly hyper-hydroxymethylated. A binary linear classifier predicting cardiovascular death among 19 dizygotic pairs was identified and equivalent to that generated from MZ via the 2D transformation. Computational bioinformatics discovered path-ways, phenotypes, and DNA motifs for these DhMRs or their subtypes, suggesting that hy-droxymethylation was a pathophysiological mechanism underlying cardiovascular death that might be influenced by genetic factors and warranted further investigations of mechanisms of these signature regions in vivo and in vitro.

Original languageEnglish (US)
Article number1183
Issue number8
StatePublished - Aug 2021


  • Cardiovascular disease
  • Dizygotic
  • Hydroxymethylation
  • Monozygotic
  • Twins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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