title: Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55).
  
  
  
  One-year average ambient fine particulate matter (PM2.5) and oxides of nitrogen (NOX) concentrations were predicted at participants' (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina's Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution.
  
  
  
  At a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM2.5and none were associated with NOX. Cg20455854 had the smallest p-value for the association with PM2.5(p = 2.77 × 10-5). mRNA expression profiles of genes near three of the PM2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM2.5exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure.
  
  
  
  We observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, 1959 NE Pacific St, Box 357236, Seattle, WA, 98195, USA. glochi@uw.edu.
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Chi
authors.affiliation: Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: MacDonald
authors.affiliation: Division of General Medicine, Mailman School of Public Health, Columbia University, New York, NY, USA.|Division of Pulmonary, Allergy & Critical Care, Columbia University Medical Center, New York, NY, USA.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.affiliation: Division of General Medicine, Mailman School of Public Health, Columbia University, New York, NY, USA.|Division of Pulmonary, Allergy & Critical Care, Columbia University Medical Center, New York, NY, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Donohue
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, 1959 NE Pacific St, Box 357236, Seattle, WA, 98195, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hensley
authors.affiliation: Department of Preventive Medicine, Division of Cancer Epidemiology and Prevention, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCall
authors.affiliation: Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Reynolds
authors.affiliation: New York Academy of Medicine, New York, NY, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, 1959 NE Pacific St, Box 357236, Seattle, WA, 98195, USA.|Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Kaufman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000393:Air Pollutants / Q000032:analysis; D000397:Air Pollution / Q000032:analysis*; D050197:Atherosclerosis; D044383:Black People; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000032:analysis; D052638:Particulate Matter / Q000032:analysis; D059467:Transcriptome; D014481:United States; D044465:White People; D001741:Black or African American
chemical_list: D000393:Air Pollutants; D009589:Nitrogen Oxides; D052638:Particulate Matter
keywords: ANKHD1; ANKRD11; Air pollution; BAZ2B; DNA methylation; LGALS2; NOX; PM2.5; PPIE