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

Clinical Epigenetics

Parveen Bhatti¹  Anne E. Justice²  Stephen S. Rich³  Celina I. Valencia⁴  Kristina Jordahl⁵  Alicia Smith⁶  Karen Conneely⁷  Steve Horvath⁸  Themistocles L. Assimes⁹  Jie Yao^1,10  Jerome I. Rotter^1,10  Xiuqing Guo^1,10  David Van Den Berg^1,11  Eric A. Whitsel^1,12  Leslie Lange^1,13  Weihua Guan^1,14  Ellen Demerath^1,15  Yongmei Liu^1,16  Jingzhong Ding^1,17  Steve Nguyen^1,18  Aladdin Shadyab^1,18  Aryeh D. Stein^1,19  Lisa R. Staimez^1,19  K. M. Venkat Narayan^1,19  Whitney L. Do^2,20 

[1] Cancer Control Research, BC Cancer, Vancouver, BC, Canada;Center for Biomedical and Translational Informatics, Geisinger, Wilkes-Barre, PA, USA;Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA;College of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA;Department of Epidemiology, University of Washington, Seattle, WA, USA;Department of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, GA, USA;Department of Human Genetics, Emory University, Atlanta, GA, USA;Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA;Department of Medicine, Stanford University, Stanford, CA, USA;Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA;Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA;Departments of Epidemiology and Medicine, University of North Carolina, Chapel Hill, NC, USA;Division of Biomedical Informatics & Personalized Medicine, School of Medicine, Colorado University Anschutz Medical Campus, Aurora, CO, USA;Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA;Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA;Duke Molecular Physiology Institute, Duke University, Durham, NC, USA;Gerontology and Geriatric Medicine, School of Medicine, Wake Forest, Winston-Salem, NC, USA;Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, CA, USA;Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA;Nutrition and Health Sciences Program, Laney Graduate School, Emory University, 1518 Clifton Rd, 30322, Atlanta, GA, USA;

关键词: DNA methylation;    Metabolically healthy;    Obesity;    Epigenetics;   

DOI  :  10.1186/s13148-021-01194-3

来源: Springer

【 摘 要 】

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 < 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.ConclusionsDifferential 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.

【 授权许可】

CC BY