Abstract

BackgroundEpidemiological studies have shown that long-term exposure to paracetamol during pregnancy is associated with attention-deficit/hyperactivity disorder (ADHD). The mechanism by which paracetamol may modulate the increased risk of developing ADHD is currently unknown. We have conducted an epigenome-wide association study (n = 384 cord blood samples) and investigated whether prenatal exposure to paracetamol is associated with DNA methylation in children diagnosed with ADHD.ResultsAnalyses identified significant differences in DNA methylation (n = 6211 CpGs) associated with prenatal exposure to paracetamol for more than 20 days in children diagnosed with ADHD compared to controls. In addition, these samples were differentially methylated compared to samples with ADHD exposed to paracetamol for less than 20 days (n = 2089 CpGs) and not exposed to paracetamol (n = 193 CpGs). Interestingly, several of the top genes ranked according to significance and effect size have been linked to ADHD, neural development, and neurotransmission. Gene ontology analysis revealed enrichment of pathways involved in oxidative stress, neurological processes, and the olfactory sensory system, which have previously been implicated in the etiology of ADHD.ConclusionsThese initial findings suggest that in individuals susceptible to ADHD, prenatal long-term exposure to paracetamol is associated with DNA methylation differences compared to controls.

Highlights

  • Epidemiological studies have shown that long-term exposure to paracetamol during pregnancy is associated with attention-deficit/hyperactivity disorder (ADHD)

  • We stratified the analyses on paracetamol exposure and ADHD separately to evaluate the associations with DNA methylation

  • Pairwise analyses of the groups exposed to paracetamol or diagnosed with ADHD (ADHD control group) alone compared to control samples revealed no significant differences in DNA methylation (FDR

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Summary

Introduction

Epidemiological studies have shown that long-term exposure to paracetamol during pregnancy is associated with attention-deficit/hyperactivity disorder (ADHD). Attention-deficit/hyperactivity disorder (ADHD) is a common childhood disorder defined by inattention, hyperactivity, and impulsivity, which impair normal functioning and development It is one of the most prevalent psychiatric disorders of childhood affecting approximately 5% of children worldwide, often continuing into adulthood [1]. Several epidemiological studies have shown that exposure to a range of putative environmental risk factors are associated with ADHD, during the prenatal and perinatal period. These factors can only be regarded as correlates because, at present, convincing evidence that the associations reflect causal relationships have not been established [12]. The mechanisms by which the environment mediates ADHD susceptibility is not well understood, but epigenetic changes may be involved [13,14,15,16,17]

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