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DNA methylation of GFI1 as a mediator of the association between prenatal smoking exposure and ADHD symptoms at 6 years: the Hokkaido Study on Environment and Children's Health

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Title: DNA methylation of GFI1 as a mediator of the association between prenatal smoking exposure and ADHD symptoms at 6 years: the Hokkaido Study on Environment and Children's Health
Authors: Miyake, Kunio Browse this author
Miyashita, Chihiro Browse this author →KAKEN DB
Ikeda-Araki, Atsuko Browse this author
Miura, Ryu Browse this author
Itoh, Sachiko Browse this author
Yamazaki, Keiko Browse this author
Kobayashi, Sumitaka Browse this author
Masuda, Hideyuki Browse this author
Ooka, Tadao Browse this author
Yamagata, Zentaro Browse this author
Kishi, Reiko Browse this author →KAKEN DB
Keywords: ADHD
Birth cohort
DNA methylation
DOHaD
GFI1
Prenatal smoking exposure
Issue Date: 7-Apr-2021
Publisher: BioMed Central
Journal Title: Clinical epigenetics
Volume: 13
Start Page: 74
Publisher DOI: 10.1186/s13148-021-01063-z
Abstract: BackgroundPrenatal smoking exposure has been associated with childhood attention-deficit/hyperactivity disorder (ADHD). However, the mechanism underlying this relationship remains unclear. We assessed whether DNA methylation differences may mediate the association between prenatal smoking exposure and ADHD symptoms at the age of 6 years.ResultsWe selected 1150 mother-infant pairs from the Hokkaido Study on the Environment and Children's Health. Mothers were categorized into three groups according to plasma cotinine levels at the third trimester: non-smokers (<= 0.21 ng/mL), passive smokers (0.21-11.48 ng/mL), and active smokers (>= 11.49 ng/mL). The children's ADHD symptoms were determined by the ADHD-Rating Scale at the age of 6 years. Maternal active smoking during pregnancy was significantly associated with an increased risk of ADHD symptoms (odds ratio, 1.89; 95% confidence interval, 1.14-3.15) compared to non-smoking after adjusting for covariates. DNA methylation of the growth factor-independent 1 transcriptional repressor (GFI1) region, as determined by bisulfite next-generation sequencing of cord blood samples, mediated 48.4% of the total effect of the association between maternal active smoking during pregnancy and ADHD symptoms. DNA methylation patterns of other genes (aryl-hydrocarbon receptor repressor [AHRR], cytochrome P450 family 1 subfamily A member 1 [CYP1A1], estrogen receptor 1 [ESR1], and myosin IG [MYO1G]) regions did not exert a statistically significant mediation effect.ConclusionsOur findings demonstrated that DNA methylation of GFI1 mediated the association between maternal active smoking during pregnancy and ADHD symptoms at the age of 6 years.
Type: article
URI: http://hdl.handle.net/2115/81598
Appears in Collections:環境健康科学研究教育センター (Center for Environmental and Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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