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Environ Int. 2019 Nov;132:104723. doi: 10.1016/j.envint.2019.03.071. Epub 2019 Jun 14.

Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation.

Author information

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
Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences and Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.
7
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
8
Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
9
Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, 104 Mason Farm Rd, Chapel Hill, NC, USA.
10
Institute of Epidemiology, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany.
11
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany.
12
Institute of Epidemiology, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany; Environmental Science Center, University of Augsburg, Augsburg, Germany.
13
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, CA, USA.
14
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
15
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
16
Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
17
Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
18
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
19
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.
20
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
21
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.
22
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, Evanston, IL, USA.
23
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:

DNA methylation (DNAm) may contribute to processes that underlie associations between air pollution and poor health. Therefore, our objective was to evaluate associations between DNAm and ambient concentrations of particulate matter (PM) ≤2.5, ≤10, and 2.5-10 μm in diameter (PM2.5; PM10; PM2.5-10).

METHODS:

We conducted a methylome-wide association study among twelve cohort- and race/ethnicity-stratified subpopulations from the Women's Health Initiative and the Atherosclerosis Risk in Communities study (n = 8397; mean age: 61.5 years; 83% female; 45% African American; 9% Hispanic/Latino American). We averaged geocoded address-specific estimates of daily and monthly mean PM concentrations over 2, 7, 28, and 365 days and 1 and 12 months before exams at which we measured leukocyte DNAm in whole blood. We estimated subpopulation-specific, DNAm-PM associations at approximately 485,000 Cytosine-phosphate-Guanine (CpG) sites in multi-level, linear, mixed-effects models. We combined subpopulation- and site-specific estimates in fixed-effects, inverse variance-weighted meta-analyses, then for associations that exceeded methylome-wide significance and were not heterogeneous across subpopulations (P < 1.0 × 10-7; PCochran's Q > 0.10), we characterized associations using publicly accessible genomic databases and attempted replication in the Cooperative Health Research in the Region of Augsburg (KORA) study.

RESULTS:

Analyses identified significant DNAm-PM associations at three CpG sites. Twenty-eight-day mean PM10 was positively associated with DNAm at cg19004594 (chromosome 20; MATN4; P = 3.33 × 10-8). One-month mean PM10 and PM2.5-10 were positively associated with DNAm at cg24102420 (chromosome 10; ARPP21; P = 5.84 × 10-8) and inversely associated with DNAm at cg12124767 (chromosome 7; CFTR; P = 9.86 × 10-8). The PM-sensitive CpG sites mapped to neurological, pulmonary, endocrine, and cardiovascular disease-related genes, but DNAm at those sites was not associated with gene expression in blood cells and did not replicate in KORA.

CONCLUSIONS:

Ambient PM concentrations were associated with DNAm at genomic regions potentially related to poor health among racially, ethnically and environmentally diverse populations of U.S. women and men. Further investigation is warranted to uncover mechanisms through which PM-induced epigenomic changes may cause disease.

KEYWORDS:

Air pollution; DNA methylation; Epigenetics; Epigenome-wide association study; Particulate matter

PMID:
31208937
PMCID:
PMC6754789
[Available on 2020-11-01]
DOI:
10.1016/j.envint.2019.03.071
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