DNA methylation is associated with prenatal exposure to sulfur dioxide and childhood attention-deficit hyperactivity disorder symptoms

Epigenetic influence plays a role in the association between exposure to air pollution and attention deficit hyperactivity disorder (ADHD); however, research regarding sulfur dioxide (SO 2 ) is scarce. Herein, we investigate the associations between prenatal SO 2 exposure and ADHD rating scale (ARS) at ages 4, 6 and 8 years repeatedly in a mother–child cohort (n = 329). Whole blood samples were obtained at ages 2 and 6 years, and genome-wide DNA methylation (DNAm) was analyzed for 51 children using the Illumina Infinium HumanMethylation BeadChip. We analyzed the associations between prenatal SO 2 exposure and DNAm levels at ages 2 and 6, and further investigated the association between the DNAm and ARS at ages 4, 6 and 8. Prenatal SO 2 exposure was associated with ADHD symptoms. From candidate gene analysis, DNAm levels at the 6 CpGs at age 2 were associated with prenatal SO 2 exposure levels. Of the 6 CpGs, cg07583420 ( INS-IGF2 ) was persistently linked with ARS at ages 4, 6 and 8. Epigenome-wide analysis showed that DNAm at 6733 CpG sites were associated with prenatal SO 2 exposure, of which 58 CpGs involved in Notch signalling pathway were further associated with ARS at age 4, 6 and 8 years, persistently. DNAm at age 6 was not associated with prenatal SO 2 exposure. Changes in DNAm levels associated with prenatal SO 2 exposure during early childhood are associated with increases in ARS in later childhood.