title: Differential DNA methylation and PM2.5species in a 450K epigenome-wide association study.
abstract: Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM2.5species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects. Bonferroni correction was applied to adjust for multiple comparisons. Bioinformatics analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was also performed. We observed 20 Bonferroni significant (P-value < 9.4× 10-9) CpGs for Fe, 8 for Ni, and 1 for V. Particularly, methylation at Schlafen Family Member 11 (SLFN11) cg10911913 was positively associated with measured levels of all 3 species. The SLFN11 gene codes for an interferon-induced protein that inhibits retroviruses and sensitizes cancer cells to DNA-damaging agents. Bioinformatics analysis suggests that gene targets may be relevant to pathways including cancers, signal transduction, and cell growth and death. Ours is the first study to examine the epigenome-wide association between ambient particles species and DNA methylation. We found that long-term exposures to specific components of ambient particle pollution, especially particles emitted during oil combustion, were associated with methylation changes in genes relevant to immune responses. Our findings provide insight into potential biologic mechanisms on an epigenetic level.
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Lingzhen
authors.initials: L
authors.lastname: Dai
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Amar
authors.initials: A
authors.lastname: Mehta
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Mordukhovich
authors.affiliation: b Department of Preventive Medicine , Icahn School of Medicine at Mount Sinai , New York , NY , USA.
authors.forename: Allan C
authors.initials: AC
authors.lastname: Just
authors.affiliation: c Department of Biostatistics , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Shen
authors.affiliation: d Department of Preventive Medicine , Feinberg School of Medicine, Northwestern University , Chicago , IL , USA.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.affiliation: e Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System , Department of Medicine, Boston University School of Medicine , Boston , MA , USA.
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.affiliation: e Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System , Department of Medicine, Boston University School of Medicine , Boston , MA , USA.
authors.forename: Pantel S
authors.initials: PS
authors.lastname: Vokonas
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008670:Metals / Q000032:analysis; D009687:Nuclear Proteins / Q000235:genetics; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*
chemical_list: D008670:Metals; D009687:Nuclear Proteins; D052638:Particulate Matter; C576668:SLFN11 protein, human
keywords: Ambient particulate matter; DNA methylation; epigenome-wide association study; metals; pathway enrichment