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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gondalia, R; Baldassari, A; Holliday, KM; Justice, AE; Méndez-Giráldez, R; Stewart, JD; Liao, D; Yanosky, JD; Brennan, KJM; Engel, SM; Jordahl, KM; Kennedy, E; Ward-Caviness, CK; Wolf, K; Waldenberger, M; Cyrys, J; Peters, A; Bhatti, P; Horvath, S; Assimes, TL; Pankow, JS; Demerath, EW; Guan, W; Fornage, M; Bressler, J; North, KE; Conneely, KN; Li, Y; Hou, L; Baccarelli, AA; Whitsel, EA

Published Date

  • June 14, 2019

Published In

Start / End Page

  • 104723 -

PubMed ID

  • 31208937

Pubmed Central ID

  • 31208937

Electronic International Standard Serial Number (EISSN)

  • 1873-6750

Digital Object Identifier (DOI)

  • 10.1016/j.envint.2019.03.071

Language

  • eng

Conference Location

  • Netherlands