Causal role of immune cells in obstructive sleep apnea hypopnea syndrome: Mendelian randomization study

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.