Tong Yao, Chen Yan-Jing, Cui Guang-Bin
Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, Shaanxi Province, China.
Department of Radiology, Peking University Third Hospital, Beijing, China.
BMC Psychiatry. 2025 May 6;25(1):454. doi: 10.1186/s12888-025-06899-w.
Attention deficit hyperactivity disorder (ADHD) and Obstructive sleep apnea (OSA) are highly clinically co-occurring, but the mechanisms behind this remain unclear, so this article analyzes the reasons for the co-morbidities from a genetic perspective.
We examined the genetic architecture of ADHD and OSA based on the large genome-wide association studies (GWAS). The global genetic relationship between OSA and ADHD was explored. Cross-trait analysis from single nucleotide polymorphism (SNP) and gene level was performed subsequently to detect the crucial genomic regions. Finally, we revealed the anatomical change on which genetic overlap relies and further explored whether genetic factors exert a causal effect.
After using both linkage disequilibrium score regression (LDSC) and High-definition likelihood inference (HDL) methods, we identified a significant genetic correlation between OSA and ADHD (PLDSC = 2.45E-28, PHDL = 1.09E-25), demonstrating a consistent direction. Furthermore, through the application of various cross-trait methods, we pinpointed 5 loci and 57 genes involved in regulating the co-occurrence of these disorders. These genetic regions were thought to be associated with the prefrontal lobes (P = 3.07E-06) and the nucleus accumbens basal ganglia (P = 2.85E-06). Lastly, utilizing Mendelian randomization (MR), we established a link indicating that individuals with ADHD were at an elevated risk of developing OSA (PIVM = 0.02, OR (95%CI):1.09 (1.01-1.17)).
This study reveals a strong genetic correlation between ADHD and OSA. It offers insights for future drug target development and sleep management in ADHD.
注意力缺陷多动障碍（ADHD）与阻塞性睡眠呼吸暂停（OSA）在临床上高度共现，但其背后的机制尚不清楚，因此本文从遗传学角度分析了共病的原因。
我们基于大型全基因组关联研究（GWAS）研究了ADHD和OSA的遗传结构。探索了OSA与ADHD之间的整体遗传关系。随后进行了单核苷酸多态性（SNP）和基因水平的跨性状分析，以检测关键的基因组区域。最后，我们揭示了遗传重叠所依赖的解剖学变化，并进一步探讨了遗传因素是否具有因果效应。
在使用连锁不平衡评分回归（LDSC）和高清似然推断（HDL）方法后，我们确定了OSA与ADHD之间存在显著的遗传相关性（PLDSC = 2.45E-28，PHDL = 1.09E-25），显示出一致的方向。此外，通过应用各种跨性状方法，我们确定了5个位点和57个参与调节这些疾病共现的基因。这些遗传区域被认为与前额叶（P = 3.07E-06）和伏隔核基底神经节（P = 2.85E-06）有关。最后，利用孟德尔随机化（MR），我们建立了一种联系，表明患有ADHD的个体患OSA的风险增加（PIVM = 0.02，OR（95%CI）：1.09（1.01-1.17））。
本研究揭示了ADHD与OSA之间存在很强的遗传相关性。它为未来ADHD的药物靶点开发和睡眠管理提供了见解。
