Unique Associations of DNA Methylation Regions with 24-Hour Blood Pressure Phenotypes in Blacks

Michelle L. Roberts, Theodore A. Kotchen, Xiaoqing Pan, Yingchuan Li, Chun Yang, Pengyuan Liu, Tao Wang, Purushottam W. Laud, Thomas H. Chelius, Yannick Munyura, David L. Mattson, Yong Liu, Allen W. Cowley, Srividya Kidambi, Mingyu Liang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Epigenetic marks (eg, DNA methylation) may capture the effect of gene-environment interactions. DNA methylation is involved in blood pressure (BP) regulation and hypertension development; however, no studies have evaluated its relationship with 24-hour BP phenotypes (daytime, nighttime, and 24-hour average BPs). Methods: We examined the association of whole blood DNA methylation with 24-hour BP phenotypes and clinic BPs in a discovery cohort of 281 Blacks using reduced representation bisulfite sequencing. We developed a deep and region-specific methylation sequencing method, Bisulfite ULtrapLEx Targeted Sequencing and utilized it to validate our findings in a separate validation cohort (n=117). Results: Analysis of 38 215 DNA methylation regions (MRs), derived from 1 549 368 CpG sites across the genome, identified up to 72 regions that were significantly associated with 24-hour BP phenotypes. No MR was significantly associated with clinic BP. Two to 3 MRs were significantly associated with various 24-hour BP phenotypes after adjustment for age, sex, and body mass index. Together, these MRs explained up to 16.5% of the variance of 24-hour average BP, while age, sex, and BMI explained up to 11.0% of the variance. Analysis of one of the MRs in an independent cohort using Bisulfite ULtrapLEx Targeted Sequencing confirmed its association with 24-hour average BP phenotype. Conclusions: We identified several MRs that explain a substantial portion of variances in 24-hour BP phenotypes, which might be excellent markers of cumulative effect of factors influencing 24-hour BP levels. The Bisulfite ULtrapLEx Targeted Sequencing workflow has potential to be suitable for clinical testing and population screenings on a large scale.

Original languageEnglish (US)
Pages (from-to)761-772
Number of pages12
JournalHypertension
Volume79
Issue number4
DOIs
StatePublished - Apr 1 2022

Keywords

  • DNA methylation
  • blood pressure
  • epigenetics
  • hypertension

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint

Dive into the research topics of 'Unique Associations of DNA Methylation Regions with 24-Hour Blood Pressure Phenotypes in Blacks'. Together they form a unique fingerprint.

Cite this