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<p>Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder modulated by genetic and environmental factors. Approximately 20–55% of individuals with ADHD experience concurrent sleep disturbances, yet the dynamic relationship between the two and their shared genetic mechanisms remain unclear. This study analyzed 11,288 participants (52.1% male) from the Adolescent Brain Cognitive Development Study using the Sleep Disturbance Scale for Children. We found a robust positive correlation between ADHD and sleep traits, though ADHD medication weakened this relationship. Latent growth curve modeling revealed that ADHD symptoms significantly impacted sleep traits with a lag effect. Polygenic risk score analyses showed significant but very small associations (explained variance ~0.28–0.30%). Pleiotropic analyses identified two loci associated with ADHD and excessive somnolence (implicating 30 genes), and cross-cohort comparisons with UK Biobank insomnia data uncovered 12 additional pleiotropic loci (98 genes) enriched in brain tissue. Functional enrichment analysis highlighted excitatory and inhibitory neuronal subtypes in visual and frontal cortices, suggesting roles in synaptic transmission and neural circuit development. Protein-protein interaction network analysis identified 10 hub genes involved in cell growth regulation and neurodevelopmental processes. This study demonstrates robust ADHD-sleep associations, with medication moderating this link, and provides preliminary insights into their shared genetic architecture.</p>

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Dynamic relationship and pleiotropic loci of attention deficit hyperactivity disorder with sleep traits

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月15日

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  • Yujuan Zu,
  • Tao Pang,
  • Lingxue Luo,
  • Chao Liufu,
  • Zixuan Xu,
  • Luxian Lv,
  • Wenqiang Li,
  • Suhua Chang

摘要

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder modulated by genetic and environmental factors. Approximately 20–55% of individuals with ADHD experience concurrent sleep disturbances, yet the dynamic relationship between the two and their shared genetic mechanisms remain unclear. This study analyzed 11,288 participants (52.1% male) from the Adolescent Brain Cognitive Development Study using the Sleep Disturbance Scale for Children. We found a robust positive correlation between ADHD and sleep traits, though ADHD medication weakened this relationship. Latent growth curve modeling revealed that ADHD symptoms significantly impacted sleep traits with a lag effect. Polygenic risk score analyses showed significant but very small associations (explained variance ~0.28–0.30%). Pleiotropic analyses identified two loci associated with ADHD and excessive somnolence (implicating 30 genes), and cross-cohort comparisons with UK Biobank insomnia data uncovered 12 additional pleiotropic loci (98 genes) enriched in brain tissue. Functional enrichment analysis highlighted excitatory and inhibitory neuronal subtypes in visual and frontal cortices, suggesting roles in synaptic transmission and neural circuit development. Protein-protein interaction network analysis identified 10 hub genes involved in cell growth regulation and neurodevelopmental processes. This study demonstrates robust ADHD-sleep associations, with medication moderating this link, and provides preliminary insights into their shared genetic architecture.