Combined Association Between ADIPOQ, PPARG, and TNF Genes Variants and Obstructive Sleep Apnea in Chinese Han Population

Abstract

Purpose: Obstructive sleep apnea (OSA) is a common chronic polygenic disease. Multiple genetic markers associated with OSA have been identified by genome-wide association studies. Here, we aimed to construct a polygenic risk score (PRS) and examine the association with the presence of OSA in a Chinese Han Population. Patients and Methods: This study included 1057 individuals who were genotyped for nine susceptibility loci from three genes (ADIPOQ, PPARG, and TNF), from which each individual’s PRS was calculated by summing the number of risk alleles. The associations between PRS and OSA were determined by logistic regression analyses. Model discrimination was assessed by a receiver operating characteristic (ROC) curve using bootstrapping with 1000 resamples. Results: The subjects included 874 with OSA and 183 controls. A higher PRS was associated with an increased apnea-hypopnea index (AHI). The PRS was an important risk factor for the development of OSA (OR = 1.237 per SD, P = 0.030). Subjects with higher PRS had a 2.88-fold (95% CI: 1.393–5.955, P = 0.004) and 5.402-fold (95% CI: 2.311–12.624, P<0.001) greater risk for having OSA and moderate-to-severe OSA, respectively, compared with those with lower genetic risk. More importantly, compared with determina-tion of risk based solely on clinical factors, addition of the PRS increased discriminatory accuracy for both OSA (AUC from 0.75 to 0.78, P = 0.02) and moderate-to-severe OSA (AUC from 0.80 to 0.83, P = 0.02). Conclusion: Our study suggests that the PRS is independently associated with AHI and OSA. Combining PRS with conventional risk factors could improve the discrimination of OSA.