Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n = 876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g., P-value threshold < 0.05, β [SE], 5.815 [1.774]; P = 0.002) and inattention domain (e.g., P-value threshold < 0.05, β [SE], 5.734 [1.761]; P = 0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD.

注意缺陷多动障碍 (ADHD) 是一种高度遗传的神经发育障碍，在 ADHD 患者中经常观察到白天过度嗜睡。白天过度嗜睡也是发作性睡病和原发性嗜睡症 (EHS) 的核心症状，它们也是遗传性疾病。精神兴奋剂对 ADHD（主要推荐干预）和两种睡眠障碍（经常标签外使用）的症状控制有效。然而，这些疾病的共同生物学机制尚未得到很好的理解。使用先前收集的发作性睡病和 EHS 的全基因组关联研究，我们计算了每个人的多基因风险评分 (PRS)。我们在滨松出生队列的母亲和儿童（HBC 研究）中调查了 ADHD 和发作性睡病特征之间可能的遗传关联。n  = 876）。基因集富集分析用于确定这些疾病的常见途径。发作性睡病 PRS 与多动领域（例如，P值阈值 < 0.05，β [SE]，5.815 [1.774]；P  = 0.002）和注意力不集中（例如，P值阈值 < 0.05， β [SE], 5.734 [1.761]; P = 0.004）。然而，EHS PRS 与 ADHD 特征的任一域都没有显着相关性。基因集富集分析显示，与多巴胺能信号、免疫系统、铁代谢和神经胶质细胞功能相关的通路与 ADHD 和发作性睡病有关。研究结果表明，多动症和发作性睡病在遗传上是相关的，这种关系可能存在共同的潜在生物学机制。未来的研究将有必要复制这些发现，以阐明 ADHD 患者白天嗜睡的遗传脆弱性。