已发表论文

在基因层面上肺动脉高压、睡眠障碍和脑结构之间的三角因果关系:一项以肺脑轴为重点的孟德尔随机化研究

 

Authors Zhang C, Su X, Zhang Y, He P, Kong X, Zhang Z, Wei Y, Shi Y

Received 6 October 2024

Accepted for publication 11 February 2025

Published 21 February 2025 Volume 2025:17 Pages 343—356

DOI https://doi.org/10.2147/NSS.S495071

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Ahmed BaHammam

Chenwei Zhang,1,2 Xuesen Su,1,2 Yukai Zhang,2 Peiyun He,2 Xiaomei Kong,1 Zhenxia Zhang,1 Yangyang Wei,1 Yiwei Shi1,2 

1NHC Key Laboratory of Pneumoconiosis, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2First School of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China

Correspondence: Yangyang Wei; Yiwei Shi, NHC Key Laboratory of Pneumoconiosis, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China, Email 512266595@qq.com; shiyw@sxmu.edu.cn

Background: The bidirectional relationship between pulmonary hypertension (PH) and sleep disorders has attracted significant research attention. The concept of the lung-brain axis has further highlighted the need for a holistic approach to managing these diseases.
Methods: This study used bidirectional two-sample Mendelian Randomization (MR) to explore the genetic-level causal relationships between PH, sleep disorders, and structural brain changes. GWAS data for PH were pooled from four cohorts; data on four sleep disorder subtypes were sourced from the FinnGen database; and data on 15 structural brain changes were obtained from the ENIGMA Consortium. To ensure reliability, we applied strict data selection, multiple corrections, heterogeneity assessments, and sensitivity tests. Visualizations included forest plots, scatter plots, funnel plots, and leave-one-out plots.
Results: MR analysis revealed a significant causal relationship between PH and both obstructive sleep apnea (OSA) (OR = 1.022, 95% CI = 1.006– 1.039, P = 0.006, PBonferroni = 0.025) and general sleep disorders (OR = 1.018, 95% CI = 1.003– 1.033, P = 0.018, PFDR = 0.036), with no evidence of reverse causation and multivariable MR analyses also demonstrated significant results. PH was linked to changes in total brain volume (P = 0.032) and cerebral white matter (P = 0.035). Amygdala changes appeared to reduce the risk of sleep disorders (P = 0.008) and OSA (P = 0.014). Sensitivity analyses showed no heterogeneity, pleiotropy, or significant outliers.
Conclusion: This study identifies significant causal links between PH, sleep disorders, and structural brain changes, establishing a triangular cyclic relationship that supports the lung-brain axis concept. These findings inform clinical management of PH and its comorbidities.

Keywords: pulmonary hypertension, sleep disorders, obstructive sleep apnea, brain structure, lung-brain axis, genetic associations