DNA methylation at insulin-insulin like growth factor 2 is associated with prenatal exposure to sulfur dioxide and childhood attention-deficit hyperactivity disorder symptoms

Abstract

Backgrounds: Epigenetic influence plays a role in the association between exposure to air pollution and attention deficit hyperactivity disorder (ADHD); however, research regarding sulfur dioxide (SO2) is scarce. Herein, we investigate the associations between prenatal SO2 exposure and ADHD rating scale (ARS) scores 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 SO2 exposure and DNAm levels at ages 2 and 6, and investigated the association between the DNAm levels at the significant CpGs and ARS at ages 4, 6, and 8. Weighted gene co-methylation network analysis was conducted to detect modules weighted for prenatal SO2 exposure and ARS.Results: Prenatal SO2 exposure was associated with ADHD symptoms. DNAm levels at the 6 CpGs (cg07583420 (INS-IGF2), cg05075097 (INS-IGF2), cg25163476 (INS-IGF2), cg20296524 (TARBP1), cg15705054 (PBXIP1), and cg05951817 (SLC6A4)) at age 2 were associated with prenatal SO2 exposure levels; however, DNAm at age 6 was not associated with prenatal SO2 exposure. Of the 6 CpGs, 5 were grouped into a module correlated with prenatal SO2 exposure and ARS, of which cg07583420 (INS-IGF2) was persistently linked with ARS at ages 4, 6, and 8. Conclusions: Changes in DNAm levels associated with prenatal SO2 exposure during early childhood are linked to increases in ARS in later childhood.