Fine particle exposure changes DNA methylation within days and weeks: Discovering novel systemic pathways using a genome-wide approach.

BACKGROUND: Many epidemiological studies have shown that particulate matter (PM) concentrations are associated with an increase of respiratory and cardiovascular diseases, as well as lung cancer. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites.  RESULTS: We collected whole blood samples from three independent studies, KORA F3 (2004-05) and F4 (2006-08) from Germany and NAS (1999-2007) from US, 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. Random-effect meta-analysis was performed to pool the study-specific results and revealed 13 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (one for 2-day average, two for 7-day and ten for 28-day) at a genome-wide Bonferroni significance level (p<=7.5E-8). Five of these sites showed homogeneous associations across the three studies, both sites from the 7-day average results and 3 for the 28-day average. 10 out of 13 expressed increased methylation and there was no overlap of significant sites between the models for the three different trailing averages.  CONCLUSION: The PM-related CpG sites found in our study suggest novel plausible systemic pathways between ambient particulate matter exposure and adverse health effect through DNA methylation variations