Faculty Collaboration Database

Unique Associations of DNA Methylation Regions With 24-Hour Blood Pressure Phenotypes in Black Participants. Hypertension 2022 Apr;79(4):761-772

Date

01/08/2022

Pubmed ID

34994206

Pubmed Central ID

PMC8917053

DOI

10.1161/HYPERTENSIONAHA.121.18584

Scopus ID

2-s2.0-85126152389 (requires institutional sign-in at Scopus site)   11 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 participants 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.

Author List

Roberts ML, Kotchen TA, Pan X, Li Y, Yang C, Liu P, Wang T, Laud PW, Chelius TH, Munyura Y, Mattson DL, Liu Y, Cowley AW Jr, Kidambi S, Liang M

Authors

Thomas H. Chelius Biostatistician I in the Institute for Health and Equity department at Medical College of Wisconsin
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Srividya Kidambi MD Sr Medical Director, Chief, Professor in the Medicine department at Medical College of Wisconsin
Purushottam W. Laud PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Blood Pressure
CpG Islands
DNA Methylation
Gene-Environment Interaction
Humans
Hypertension
Phenotype