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Holliday, K.M.* ; Gondalia, R.* ; Baldassari, A.* ; Justice, A.E.* ; Stewart, J.D.* ; Liao, D.* ; Yanosky, J.D.* ; Jordahl, K.M.* ; Bhatti, P.* ; Assimes, T.L.* ; Pankow, J.S.* ; Guan, W.* ; Fornage, M.* ; Bressler, J.* ; North, K.E.* ; Conneely, K.N.* ; Li, Y.* ; Hou, L.* ; Vokonas, P.S.* ; Ward-Caviness, C.K.* ; Wilson, R. ; Wolf, K. ; Waldenberger, M. ; Cyrys, J. ; Peters, A. ; Boezen, H.M.* ; Vonk, J.M.* ; Sayols-Baixeras, S.* ; Lee, M.* ; Baccarelli, A.A.* ; Whitsel, E.A.*

Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults.

Environ. Res. 212:113360 (2022)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO2; NOx), ozone (O3), and sulfur dioxide (SO2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation- and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR<0.05) at Cytosine-phosphate-Guanine (CpG) sites without among-strata heterogeneity (PCochran's Q > 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a −0.3 (95% CI: −0.4, −0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a −0.3 (95% CI: −0.4, −0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gaseous air pollution-induced DNAm changes near genes relevant for cardiovascular and lung disease. Further harmonized investigations with a range of gaseous pollutants and averaging durations are needed to determine the effect of gaseous air pollutants on DNA methylation and ultimately gene expression.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Air Pollution ; Dna Methylation ; Epigenetics ; Epigenome-wide Association Study ; Gaseous Pollutants
ISSN (print) / ISBN 0013-9351
e-ISSN 1096-0953
Zeitschrift Environmental Research
Quellenangaben Band: 212, Heft: Pt C, Seiten: , Artikelnummer: 113360 Supplement: ,
Verlag Elsevier
Verlagsort San Diego, Calif.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)