title: Genome-Wide Analysis of DNA Methylation and Fine Particulate Matter Air Pollution in Three Study Populations: KORA F3, KORA F4, and the Normative Aging Study.
abstract: Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites.
  
  
  
  We studied the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for additional investigation.
  
  
  
  We collected whole blood samples from three independent studies-KORA F3 (2004-2005) and F4 (2006-2008) in Germany, and the Normative Aging Study (1999-2007) in the United States-and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results.
  
  
  
  Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p ≤ 7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of I2 for homogeneity assessment across the studies, 4 of these sites (annotated in NSMAF, C1orf212, MSGN1, NXN) showed p > 0.05 and I2 < 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively.
  
  
  
  The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation.
  
  
  
  Panni T, Mehta AJ, Schwartz JD, Baccarelli AA, Just AC, Wolf K, Wahl S, Cyrys J, Kunze S, Strauch K, Waldenberger M, Peters A. 2016. A genome-wide analysis of DNA methylation and fine particulate matter air pollution in three study populations: KORA F3, KORA F4, and the Normative Aging Study. Environ Health Perspect 124:983-990; http://dx.doi.org/10.1289/ehp.1509966.
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Panni
authors.forename: Amar J
authors.initials: AJ
authors.lastname: Mehta
authors.forename: Joel D
authors.initials: JD
authors.lastname: Schwartz
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.forename: Allan C
authors.initials: AC
authors.lastname: Just
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wolf
authors.forename: Simone
authors.initials: S
authors.lastname: Wahl
authors.forename: Josef
authors.initials: J
authors.lastname: Cyrys
authors.forename: Sonja
authors.initials: S
authors.lastname: Kunze
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
mesh_terms: D000393:Air Pollutants / Q000032:analysis*; D000397:Air Pollution / Q000706:statistics & numerical data*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D019175:DNA Methylation; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D055106:Genome-Wide Association Study; D005858:Germany / Q000453:epidemiology; D006801:Humans; D052638:Particulate Matter / Q000032:analysis*; D012140:Respiratory Tract Diseases / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter