The genetic overlap and causal relationship between attention deficit hyperactivity disorder and obstructive sleep apnea: a large-scale genomewide cross-trait analysis

Abstract Background 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. Methods We examined the gen...

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Bibliographic Details
Main Authors: Yao Tong, Yan-Jing Chen, Guang-Bin Cui
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06899-w
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Summary:Abstract Background 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. Methods 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. Results 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)). Conclusions This study reveals a strong genetic correlation between ADHD and OSA. It offers insights for future drug target development and sleep management in ADHD.
ISSN:1471-244X