Objectives This study aimed to investigate the impact of Obstructive Sleep Apnea (OSA) on immune cell profiles by utilizing both the National Health and Nutrition Examination Survey (NHANES) dataset and a two-sample Mendelian Randomization (MR) method. Methods We included 20,732 participants from the NHANES to explore the relationship between symptom defined OSA and peripheral immune cells. Additionally, we conducted a two-sample MR analysis to investigate the effect of OSA on 35 summarized peripheral immune cell properties and 731 immunophenotypes. To ensure the robustness of findings in MR analysis, we conducted a sensitivity analysis. Results The NHANES dataset and MR analysis indicated that OSA patients exhibit significantly elevated levels of white blood cells, neutrophils, and granulocytes, along with lower levels of lymphocytes. Furthermore, the MR analysis demonstrated a causal link between genetic predisposition to OSA and ten lymphocyte subtypes. Notably, there is a decrease in CD3 expression on Natural Killer-T (NKT) cells ( β IVW = −0.47, SE = 0.17, p = 0.005), and an increase in lgD expression on lgD + CD38+ B-cells ( β IVW = 0.36, SE = 0.15, p = 0.020) among individuals with a genetic predisposition to OSA. No heterogeneity or pleiotropy was identified. Conclusion OSA is associated with elevated neutrophils, granulocytes, and systemic immune-inflammation index. Causally, OSA reduces NKT cells and disrupts lymphocyte homeostasis, impairing B-cell maturation/activation. These immune signatures may serve as clinical biomarkers for guide risk stratification and guide personalized therapies, including targeted immunomodulation. Level of evidence This study combined a cross-sectional analysis of NHANES datasets with a Mendelian Randomization (MR) approach utilizing GWAS datasets. The MR analysis provides a level of evidence second only to randomized controlled trials, surpassing that of cohort and case-control studies.
Jia et al. (2026) studied this question.