Zhao HH, Ma Z, Guan DS. Causal role of immune cells in obstructive sleep apnea hypopnea syndrome: Mendelian randomization study. World J Clin Cases 2024; 12(7): 1227-1234 [PMID: 38524502 DOI: 10.12998/wjcc.v12.i7.1227]
Corresponding Author of This Article
Zhen Ma, Doctor, Researcher, Department of Personnel, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, No. 19 Renmin Road, Jinshui District, Zhengzhou 450000, Henan Province, China. mz15903698623@163.com
Research Domain of This Article
Immunology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Cases. Mar 6, 2024; 12(7): 1227-1234 Published online Mar 6, 2024. doi: 10.12998/wjcc.v12.i7.1227
Causal role of immune cells in obstructive sleep apnea hypopnea syndrome: Mendelian randomization study
Huang-Hong Zhao, Zhen Ma, Dong-Sheng Guan
Huang-Hong Zhao, Department of Encephalopathy, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
Zhen Ma, Department of Personnel, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
Dong-Sheng Guan, Department of Neurology, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
Author contributions: Zhao HH assisted with planning, directing, and writing, as well as with editing and revising; Ma Z helped with the first draft of the writing, the formal analysis, and the data collection; Guan DS helped with the statistical analysis; the essay was written by all writers, who also gave their approval to the final draft.
Supported byDoctoral Research Fund Project of Henan Provincial Hospital of Traditional Chinese Medicine, No. 2022BSJJ10.
Institutional review board statement: The selected GWAS data is obtained from open-source databases, specifically the NHGRI-EBI Catalog (https://www.ebi.ac.uk/gwas/). As it originates from such sources, there is no "Institutional Review Board statement" associated with it.
Informed consent statement: Consent was not needed as the study was retrospective without exposure to the patients’ data.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
Data sharing statement: Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhen Ma, Doctor, Researcher, Department of Personnel, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, No. 19 Renmin Road, Jinshui District, Zhengzhou 450000, Henan Province, China. mz15903698623@163.com
Received: November 22, 2023 Peer-review started: November 22, 2023 First decision: December 23, 2023 Revised: February 2, 2024 Accepted: January 29, 2024 Article in press: January 29, 2024 Published online: March 6, 2024 Processing time: 99 Days and 16.6 Hours
ARTICLE HIGHLIGHTS
Research background
Despite being one of the most prevalent sleep disorders, obstructive sleep apnea hypoventilation syndrome (OSAHS) has limited information on its immunologic foundation. The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies (GWAS) and genotyping techniques using high-density genetic markers (e.g., SNPs or CNVs). But this tactic hasn't yet been applied to OSAHS. Using a Mendelian randomization analysis, we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS.
Research motivation
In summary, our comprehensive bidirectional mendelian randomization (MR) analysis has revealed causal links between various immunophenotypes and OSAHS, shedding light on the intricate web of relationships between OSAHS and the immune system. Moreover, Reverse causality, other variables, and other unavoidable confounding factors have all been successfully reduced in impact by our study, offering a fresh perspective for researchers to delve into the biological underpinnings of OSAHS and potentially pave the way for early intervention and treatment strategies. These findings expand the realm of psychoimmunology and offer valuable insights for OSAHS prevention.
Research objectives
This study employed two-sample Mendelian randomization analysis using data from a large genomic research cohort of approximately 372657 individuals, assuring great statistical efficiency. The outcomes of the study were based on genetic instrumental variables, and causal inferences were conducted by various robust Mendelian randomization analysis techniques, which were unaffected by horizontal pleiotropy and other variables. This study does have several drawbacks, though. First, a thorough evaluation of horizontal pleiotropy is still difficult to achieve, even after several sensitivity studies. Second, stratified population analyses were not feasible due to the lack of individual-level data. Third, the study's reliance on European databases limits the generalizability of the findings to other ethnic groups. Finally, the study's flexible outcome assessment criteria may have led to more false positives, but they also made it easier to evaluate the full extent of the strong relationship between immunological traits and OSAHS.
Research methods
A comprehensive two-sample MR study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS. Summary statistics for each immune cell feature were obtained from the GWAS catalog. Information on 731 immune cell properties, such as morphologic parameters, median fluorescence intensity, absolute cellular, and relative cellular, was compiled using publicly available genetic databases. The results' robustness, heterogeneity, and horizontal pleiotropy were confirmed using extensive sensitivity examination.
Research results
After false discovery rate correction, OSAHS had no statistically significant effect on immunophenotypes. However, Two lymphocyte subsets were identified to be significantly associated with OSAHS risk: (OR = 1.03, 95%CI = 1.01-1.03, P = 0.000); CD28+CD4+T cell (OR = 1.04, 95%CI = 1.02-1.04, P = 0.019).
Research conclusions
The study has shown the close association between immune cells and OSAHS through genetic methods, thereby offering direction for future clinical research.
Research perspectives
This groundbreaking study employs bidirectional MR analysis to unveil crucial immunological links in OSAHS. By establishing causal relationships between diverse immunophenotypes and OSAHS, the research offers a fresh lens for exploring the disorder's biological foundations. Successfully addressing confounding factors, the study presents opportunities for early intervention and insights into targeted preventive strategies. While limitations exist, including challenges in evaluating horizontal pleiotropy and generalizability, identifying specific lymphocyte subsets strengthens the convergence of immunology and OSAHS research, guiding future clinical investigations with promising avenues for intervention.