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)
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.
Impact Factor
Scopus SNIP
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Times Cited
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Air Pollution ; Dna Methylation ; Epigenetics ; Epigenome-wide Association Study ; Gaseous Pollutants
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2022
Prepublished im Jahr
0
HGF-Berichtsjahr
2022
ISSN (print) / ISBN
0013-9351
e-ISSN
1096-0953
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 212,
Heft: Pt C,
Seiten: ,
Artikelnummer: 113360
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
San Diego, Calif.
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504090-001
G-504091-001
G-504000-001
G-504000-004
G-504000-010
Förderungen
Copyright
Erfassungsdatum
2022-07-04