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

• Published in: Scientific reports Vol. 13; no. 1; p. 3501
• Main Authors: Choi, Yoon-Jung, Cho, Jinwoo, Hong, Yun-Chul, Lee, Dong-wook, Moon, Sungji, Park, Soo Jin, Lee, Kyung-shin, Shin, Choong Ho, Lee, Young Ah, Kim, Bung-Nyun, Kaminsky, Zachary, Kim, Johanna Inhyang, Lim, Youn-Hee
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/174; 692/4017; Age; Air pollution; Air Pollution - adverse effects; Attention Deficit Disorder with Hyperactivity - etiology; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit hyperactivity disorder; Child; Child, Preschool; Children; CpG islands; Deoxyribonucleic acid; DNA; DNA Methylation; Epigenetics; Exposure; Female; Genomes; Humanities and Social Sciences; Humans; Insulin-like growth factor II; multidisciplinary; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects; Science; Science (multidisciplinary); Signal transduction; Sulfur; Sulfur dioxide; Sulfur Dioxide - adverse effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-29843-y

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.