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Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes.

Authors :
Do WL
Nguyen S
Yao J
Guo X
Whitsel EA
Demerath E
Rotter JI
Rich SS
Lange L
Ding J
Van Den Berg D
Liu Y
Justice AE
Guan W
Horvath S
Assimes TL
Bhatti P
Jordahl K
Shadyab A
Valencia CI
Stein AD
Smith A
Staimez LR
Conneely K
Narayan KMV
Source :
Clinical epigenetics [Clin Epigenetics] 2021 Dec 22; Vol. 13 (1), pp. 230. Date of Electronic Publication: 2021 Dec 22.
Publication Year :
2021

Abstract

Background: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health.<br />Results: The discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm β value, the risk of incident CHD increased by 9% in one site and decreased by 6-10% in two sites over 25 years.<br />Conclusions: Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health.<br /> (© 2021. The Author(s).)

Details

Language :
English
ISSN :
1868-7083
Volume :
13
Issue :
1
Database :
MEDLINE
Journal :
Clinical epigenetics
Publication Type :
Academic Journal
Accession number :
34937574
Full Text :
https://doi.org/10.1186/s13148-021-01194-3