The connections between air pollution, DNAm, and health are not limited to prenatal exposures and birth outcomes, but effects may persist into childhood. As an example of this, maternal NO2 exposure during the third trimester of pregnancy was associated with higher systolic blood pressure in children assessed at the age of 11 . However, no relationship with blood LINE1 DNAm was identified with NO2 exposure. But exposure to PM10 or O3 during the first trimester was associated with lower LINE1 DNAm at birth, while O3 exposure during the third trimester was conversely associated with higher LINE1 DNAm . These results highlight the effects of early life exposures and possible differences based upon both the type of pollutant and developmental stage at exposure. Such findings also suggest that the changes induced by air pollution exposure during pregnancy can persist well into childhood. A possible mechanism for the maintenance of the effects of exposure during pregnancy into childhood could be sustained changes in DNAm. However, other factors, such as genotype, may also contribute to shaping outcomes and, in some cases, may also affect DNAm. For example, O3 exposure during the first trimester in one study was associated with increased systolic blood pressure only in 11-year-old children with particular DNMT1 or DNMT3B isoforms . This result suggests that variants that affect essential DNAm control genes have the potential to shape responses and health effects of environmental exposures (Fig. 1). These findings also suggest that a possible mechanism underlying modulation of DNAm following exposures could be changes in the expression of key enzymes that regulate DNAm (Fig. 1).
In addition to quantile analysis, other advanced statistical methods may improve data quality and provide new insights into the relationship between air pollution and DNAm. As an example, a novel multivariate Bayesian variable selection approach was implemented on an analysis of blood DNAm data from 92 volunteers . In comparison with a conventional Bayesian variable selection approach, which identified DNAm of HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA), and IL9 as being associated with mean concentrations of black carbon for the month before each blood draw, the new approach had improved sensitivity and identified HLA-DRA, Fc fragment of IgE receptor Ig, and IL9 in association with black carbon and IL5 and CCL11 with sulfate concentrations. Advances in the analysis may lead to greater consistency in the results obtained from studies of air pollution and DNAm, given that, as indicated in Additional file 2: Table S2, there is no consistency among the top CpGs identified in the studies reviewed. 59ce067264