Exploring the shared genetic basis of attention-deficit/hyperactivity disorder and obstructive sleep apnea: A multi-omics analysis

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-04-15 DOI:10.1016/j.pnpbp.2025.111369

Yijie Huang , Chao Ju , Jie Luo , Yun Li

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引用次数: 0

Abstract

Background

Observational studies have suggested an association between attention-deficit/hyperactivity disorder (ADHD) and obstructive sleep apnea (OSA), but these findings are often inconsistent due to potential biases from medication use, and varying diagnostic criteria. Genetic analyses can help mitigate these confounding factors, providing additional evidence.

Methods

This study evaluated the genetic correlations between ADHD and OSA using Genome-wide association study (GWAS) summary data, applying linkage disequilibrium score regression (LDSC) and SUPER GeNetic cOVariance Analyzer (SUPERGNOVA). Cross-trait association and colocalization analysis identify potential pleiotropic loci. Tissue enrichment analysis and gene-level analysis of shared genes between OSA and ADHD was conducted. Additionally, bidirectional Mendelian randomization was used to assess potential causal relationships.

Results

We found significant genetic correlations between ADHD and OSA (rg = 0.309, p = 3.252E−27), and identified 8 novel pleiotropic loci through cross-trait association analysis. Tissue enrichment analysis showed that these shared genes were primarily concentrated in brain tissues, particularly in deep gray matter regions, and were associated with immune and inflammatory pathways. Forward Mendelian Randomization analysis showed that ADHD was significantly associated with the risk of OSA (OR 1.070, 95 % CI 1.013–1.130, p = 0.016), and reverse analysis showed that OSA was significantly associated with the risk of ADHD (OR 1.240, 95 % CI 1.106–1.390, p = 2.213E−4).

Conclusion

The findings of this study show a significant positive genetic correlation between ADHD and OSA and each is a risk factor for the other. Inflammation in specific brain regions may be the underlying mechanism for their comorbidity.

Abstract Image

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探索注意力缺陷/多动障碍和阻塞性睡眠呼吸暂停的共同遗传基础：多组学分析

观察性研究表明注意缺陷/多动障碍（ADHD）和阻塞性睡眠呼吸暂停（OSA）之间存在关联，但由于药物使用的潜在偏差和不同的诊断标准，这些发现往往不一致。基因分析可以帮助减轻这些混杂因素，提供额外的证据。方法本研究利用全基因组关联研究（GWAS）汇总数据，应用连锁不平衡评分回归（LDSC）和超级遗传协方差分析仪（SUPERGNOVA）评估ADHD与OSA的遗传相关性。跨性状关联和共定位分析确定了潜在的多效位点。对OSA和ADHD的共享基因进行组织富集分析和基因水平分析。此外，双向孟德尔随机化被用于评估潜在的因果关系。结果ADHD与OSA存在显著的遗传相关性（rg = 0.309, p = 3.252E−27），并通过交叉性状关联分析鉴定出8个新的多效位点。组织富集分析表明，这些共享基因主要集中在脑组织中，特别是在深部灰质区域，并与免疫和炎症途径有关。正向孟德尔随机化分析显示，ADHD与OSA发生风险显著相关（OR 1.070, 95% CI 1.013-1.130, p = 0.016），反向分析显示，OSA与ADHD发生风险显著相关（OR 1.240, 95% CI 1.106-1.390, p = 2.213E−4）。结论本研究结果显示ADHD与OSA之间存在显著的正相关遗传关系，两者互为危险因素。特定大脑区域的炎症可能是其合并症的潜在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Progress in Neuro-Psychopharmacology & Biological Psychiatry 医学-精神病学

CiteScore

12.00

自引率

1.80%

发文量

153

审稿时长

56 days

期刊介绍： Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.