Background
Obstructive sleep apnea (OSA) and inflammation are closely related. This study aimed to evaluate the associations and causal effect between C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-α) levels andOSA.
Methods
Pooled analysis was conducted to compare the expression differences of CRP and TNF-α between OSA patients with different severity and controls, and between continuous positive airway pressure (CPAP) and non-CPAP interventions for OSA patients. Using published GWAS summary statistics, we conducted a bidirectional two-sample Mendelian Randomization (MR) to estimate the causal relationships between CRP and TNF-α levels and OSA risk. Effect estimates were evaluated using inverse-variance weighted (IVW) as primary method, and several other MR methods as sensitivity analysis.
Results
Both TNF-α (WMD [95%CI] = 5.86 [4.80–6.93] pg/ml,
p
< .00001) and CRP (WMD [95%CI] = 2.66 [2.15–3.17] mg/L,
p
< .00001), showed a significant increase in OSA patients compared with controls and this increasing trend was associated with OSA severity. Besides, compared to blank control (non-CPAP), CPAP treatment can reduce high TNF-α (WMD [95%CI]= −4.44 [−4.81, −4.07]pg/ml,
p
< .00001) and CRP (WMD [95%CI]= −0.91 [−1.65, −0.17] mg/l,
p
= .02) in OSA. Moreover, the primary MR analysis by IVW showed that OSA was the genetically predicted cause of elevated CRP (estimate: 0.095; 95% CI, [0.010–0.179];
p
= .029) using six SNPs as the instrument variable, which were repeated by weighted median (estimate: 0.053; 95% CI, [0.007, 0.100];
p
=.024) and MR RAPS (estimate: 0.109; 95% CI, [0.079, 0.140];
p
= 1.98x10
−12
). Besides, the causal effect from elevated CRP on increased OSA risk was almost significant by IVW (OR:1.053; 95% CI, [1.000, 1.111];
p
= .053). However, there were no causal associations between TNF-α and OSA from both directions.
Conclusions
Increased CRP and TNF-α were associated with OSA severity and sensible to CPAP treatment. Also, OSA had a suggestive causal effect on elevated CRP.
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