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

Juan Li,1,2 Qianwen Lv,1 Haili Sun,1 Yunyun Yang,1,3 Xiaolu Jiao,1,3 Song Yang,1 Huahui Yu,1,3 Yanwen Qin1,3 1Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, 100029, People’s Republic of China; 2Emergency Department, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, People’s Republic of ChinaCorrespondence: Yanwen Qin, Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-10-64456529, Fax +86-10-64456095, Email qinyanwen@vip.126.com; qinyanwen@ccmu.edu.cnPurpose: 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 determination 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.Keywords: polygenic risk score, apnea-hypopnea index, single nucleotide polymorphisms, discriminatory accuracy