학술논문
Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes
Document Type
article
Author
Do, Whitney L; Nguyen, Steve; Yao, Jie; Guo, Xiuqing; Whitsel, Eric A; Demerath, Ellen; Rotter, Jerome I; Rich, Stephen S; Lange, Leslie; Ding, Jingzhong; Van Den Berg, David; Liu, Yongmei; Justice, Anne E; Guan, Weihua; Horvath, Steve; Assimes, Themistocles L; Bhatti, Parveen; Jordahl, Kristina; Shadyab, Aladdin; Valencia, Celina I; Stein, Aryeh D; Smith, Alicia; Staimez, Lisa R; Conneely, Karen; Narayan, KM Venkat
Source
Clinical Epigenetics. 13(1)
Subject
Language
Abstract
BackgroundBody 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.ResultsThe 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