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

Publication ,  Journal Article
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 ...
Published in: Clin Epigenetics
December 22, 2021

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. 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. 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.

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Published In

Clin Epigenetics

DOI

EISSN

1868-7083

Publication Date

December 22, 2021

Volume

13

Issue

1

Start / End Page

230

Location

Germany

Related Subject Headings

  • Middle Aged
  • Metabolic Diseases
  • Male
  • Humans
  • Female
  • DNA Methylation
  • Cohort Studies
  • Cardiovascular Diseases
  • Body Mass Index
  • Aged
 

Citation

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Do, W. L., Nguyen, S., Yao, J., Guo, X., Whitsel, E. A., Demerath, E., … Narayan, K. M. V. (2021). Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes. Clin Epigenetics, 13(1), 230. https://doi.org/10.1186/s13148-021-01194-3
Do, Whitney L., Steve Nguyen, Jie Yao, Xiuqing Guo, Eric A. Whitsel, Ellen Demerath, Jerome I. Rotter, et al. “Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes.Clin Epigenetics 13, no. 1 (December 22, 2021): 230. https://doi.org/10.1186/s13148-021-01194-3.
Do WL, Nguyen S, Yao J, Guo X, Whitsel EA, Demerath E, et al. Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes. Clin Epigenetics. 2021 Dec 22;13(1):230.
Do, Whitney L., et al. “Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes.Clin Epigenetics, vol. 13, no. 1, Dec. 2021, p. 230. Pubmed, doi:10.1186/s13148-021-01194-3.
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. Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes. Clin Epigenetics. 2021 Dec 22;13(1):230.
Journal cover image

Published In

Clin Epigenetics

DOI

EISSN

1868-7083

Publication Date

December 22, 2021

Volume

13

Issue

1

Start / End Page

230

Location

Germany

Related Subject Headings

  • Middle Aged
  • Metabolic Diseases
  • Male
  • Humans
  • Female
  • DNA Methylation
  • Cohort Studies
  • Cardiovascular Diseases
  • Body Mass Index
  • Aged