Bidirectional relationship between 56 peripheral inflammatory regulators and sleep apnea syndrome: A Mendelian randomization study.

BACKGROUND

Peripheral inflammation plays an potential role in both pathogenesis and outcomes of sleep apnea syndrome (SAS). However, this topic has not been explored at the genetic level.

OBJECTIVES

The aim of the study was to investigate the genetic interaction between a total of 56 peripheral inflammatory regulators and SAS, and to further reveal the genetic association of SAS-related inflammatory regulators with several neurological disorders.

METHODS

Summary data for SAS, cerebral atherosclerosis, vascular dementia and peripheral concentrations of these inflammatory regulators were collected from genome-wide association studies. Instrumental variables were extracted from these data for causal inference of exposure and outcome using Two-sample Mendelian randomization methods. All analyses were performed using R (version 3.5.2).

RESULTS

First, of the included 56 inflammatory regulators, higher IL-25 level and lower IL-23, IL-24, IL-36γ and MIP-1a levels in peripheral circulation significantly increased the risk of SAS (P<0.05). Second, SAS significantly decreased the peripheral levels of IL-17A, IL-23, IL-27, IL-36α and TRAIL (P<0.05). Third, there was no genetic relationship between SAS and other inflammatory regulators (P>0.05). Fourth, in the SAS-related inflammatory regulators mentioned above, decreased levels of IL-17A and IL-27 in peripheral circulation were significantly associated with the increased risk of cerebral atherosclerosis, and decreased level of TRAIL promoted the elevation of vascular dementia risk (P<0.05).

CONCLUSION

There was a interaction between peripheral inflammation and SAS at the genetic level. Furthermore, peripheral inflammation might involved in the mechanism for SAS causing some neurological diseases mentioned above.