Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder that often persists into adulthood. There is growing evidence that epigenetic dysregulation participates in ADHD. Given that only a limited number of epigenome-wide association studies (EWASs) of ADHD have been conducted so far and they have mainly focused on pediatric and population-based samples, we performed an EWAS in a clinical sample of adults with ADHD. We report one CpG site and four regions differentially methylated between patients and controls, which are located in or near genes previously involved in autoimmune diseases, cancer or neuroticism. Our sensitivity analyses indicate that smoking status is not responsible for these results and that polygenic risk burden for ADHD does not greatly impact the signatures identified. Additionally, we show an overlap of our EWAS findings with genetic signatures previously described for ADHD and with epigenetic signatures for smoking behavior and maternal smoking. These findings support a role of DNA methylation in ADHD and emphasize the need for additional efforts in larger samples to clarify the role of epigenetic mechanisms on ADHD across the lifespan.

注意力缺陷/多动障碍（ADHD）是一种高度遗传性的神经发育障碍，通常会持续到成年期。越来越多的证据表明表观遗传失调与多动症有关。鉴于迄今为止仅进行了有限数量的 ADHD 全表观基因组关联研究 (EWAS)，并且这些研究主要集中于儿科和人群样本，因此我们对患有 ADHD 的成人临床样本进行了 EWAS。我们报告了患者和对照之间的 1 个 CpG 位点和 4 个区域甲基化差异，这些区域位于先前与自身免疫性疾病、癌症或神经质相关的基因中或附近。我们的敏感性分析表明，吸烟状况与这些结果无关，并且 ADHD 的多基因风险负担不会对已确定的特征产生很大影响。此外，我们的 EWAS 研究结果与之前描述的 ADHD 遗传特征以及吸烟行为和母亲吸烟的表观遗传特征有重叠。这些发现支持 DNA 甲基化在 ADHD 中的作用，并强调需要在更大的样本中进行额外的努力，以阐明表观遗传机制在 ADHD 整个生命周期中的作用。