Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study

Rahul Gondalia; Antoine Baldassari; Katelyn M Holliday; Anne E Justice; James D Stewart; Duanping Liao; Jeff D Yanosky; Stephanie M Engel; David Sheps; Kristina M Jordahl; Parveen Bhatti; Steve Horvath; Themistocles L Assimes; Ellen W Demerath; Weihua Guan; Myriam Fornage; Jan Bressler; Kari E North; Karen N Conneely; Yun Li; Lifang Hou; Andrea A Baccarelli; Eric A Whitsel

doi:10.1016/j.envres.2021.111211

Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study

Environ Res. 2021 Jul:198:111211. doi: 10.1016/j.envres.2021.111211. Epub 2021 Apr 22.

Authors

Rahul Gondalia¹, Antoine Baldassari², Katelyn M Holliday³, Anne E Justice⁴, James D Stewart², Duanping Liao⁵, Jeff D Yanosky⁵, Stephanie M Engel², David Sheps⁶, Kristina M Jordahl⁷, Parveen Bhatti⁷, Steve Horvath⁸, Themistocles L Assimes⁹, Ellen W Demerath¹⁰, Weihua Guan¹¹, Myriam Fornage¹², Jan Bressler¹³, Kari E North¹⁴, Karen N Conneely¹⁵, Yun Li¹⁶, Lifang Hou¹⁷, Andrea A Baccarelli¹⁸, Eric A Whitsel¹⁹

Affiliations

¹ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. Electronic address: rahgonda@unc.edu.
² Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
³ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Department of Community and Family Medicine, Duke University School of Medicine, Durham, NC, USA.
⁴ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Geisinger Health System, Danville, PA, USA.
⁵ Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA.
⁶ Department of Epidemiology, University of Florida, Gainesville, FL, USA.
⁷ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
⁸ Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, USA.
⁹ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
¹¹ Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
¹² Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
¹³ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
¹⁴ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.
¹⁵ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
¹⁶ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA.
¹⁷ Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University Chicago, Evanston, IL, USA; Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
¹⁸ Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences and Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
¹⁹ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.

Abstract

Background: Short-duration exposure to ambient particulate matter (PM) air pollution is associated with cardiac autonomic dysfunction and prolonged ventricular repolarization. However, associations with sub-chronic exposures to coarser particulates are relatively poorly characterized as are molecular mechanisms underlying their potential relationships with cardiovascular disease.

Materials and methods: We estimated associations between monthly mean concentrations of PM < 10 μm and 2.5-10 μm in diameter (PM_10; PM_2.5-10) with time-domain measures of heart rate variability (HRV) and QT interval duration (QT) among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities Study (n_HRV = 82,107; n_QT = 76,711). Then we examined mediation of the PM-HRV and PM-QT associations by DNA methylation (DNAm) at three Cytosine-phosphate-Guanine (CpG) sites (cg19004594, cg24102420, cg12124767) with known sensitivity to monthly mean PM concentrations in a subset of the participants (n_HRV = 7,169; n_QT = 6,895). After multiply imputing missing PM, electrocardiographic and covariable data, we estimated associations using attrition-weighted, linear, mixed, longitudinal models adjusting for sociodemographic, behavioral, meteorological, and clinical characteristics. We assessed mediation by estimating the proportions of PM-HRV and PM-QT associations mediated by DNAm.

Results: We found little evidence of PM-HRV association, PM-QT association, or mediation by DNAm.

Conclusions: The findings suggest that among racially/ethnically and environmentally diverse U.S. populations, sub-chronic exposures to coarser particulates may not exert appreciable, epigenetically mediated effects on cardiac autonomic function or ventricular repolarization. Further investigation in better-powered studies is warranted, with additional focus on shorter duration exposures to finer particulates and non-electrocardiographic outcomes among relatively susceptible populations.

Keywords: DNA methylation; Heart rate variability; Mediation; Particulate matter; QT interval Duration.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Air Pollutants* / analysis
Air Pollutants* / toxicity
Air Pollution* / adverse effects
Air Pollution* / analysis
Atherosclerosis* / chemically induced
Atherosclerosis* / epidemiology
Atherosclerosis* / genetics
Environmental Exposure / adverse effects
Environmental Exposure / analysis
Female
Humans
Male
Particulate Matter / analysis
Particulate Matter / toxicity
Women's Health

Substances

Air Pollutants
Particulate Matter

Abstract

Publication types

MeSH terms

Substances

Grants and funding