Road traffic noise exposure and blood DNA methylation at birth and in childhood: An epigenome-wide meta-analysis.

Road traffic noise exposure has been associated with multiple adverse outcomes in epidemiological studies. However, the underlying biological mechanisms remain unclear. The aim of this study was to investigate the association between road traffic noise exposure and cord blood and child blood DNA methylation (DNAm). Data from six European studies (BAMSE, Generation R, HELIX, INMA, LISA, PIAMA) were used to perform the discovery epigenome-wide meta-analysis. Prenatal, infancy, and recent road traffic noise exposure was assessed at the residential addresses. Blood DNAm was measured using the Illumina 450 K or EPIC arrays. To identify differentially methylated positions (DMPs), we fitted robust linear regression models for each cohort, and the results were subsequently meta-analyzed. Differentially methylated regions (DMRs) were identified using Comb-p and DMRcate. Findings were then looked-up in the independent ALSPAC cohort, in which noise was measured categorically. A total of 1477 newborns with DNAm data in cord blood, and 1129 and 2065 with DNAm in child blood (age 4-6 and age 8-10 years, respectively) were included in the discovery meta-analysis. We did not observe genome-wide significant (False Discovery Rate (FDR) < 0.05) DMPs associated with road traffic noise exposure. However, 46 DMPs reached suggestive significance (P < 1 × 10-5) across different time windows. One CpG site (cg09400092, annotated to SSTR1) associated with recent noise exposure at age 8-10 years was also significantly associated in the ALSPAC cohort (same direction of association with P = 0.00165). In addition, we identified a total of 93 FDR significant DMRs, of which 14 were nominally significant in the ALSPAC study. In conclusion, we observed suggestive evidence of an association between road traffic noise exposure and DNAm in child blood. This may indicate that differential DNAm plays a role in the biological mechanism underlying health effects of noise exposure.