Abstract:ObjectiveTo evaluate the associations of sleep, circadian rhythm gene polymorphisms and their combined effects with obstructive sleep apnea-hypopnea syndrome(OSAHS). Methods The sleep and circadian rhythm-related genes were collected from public databases and existing literatures to explore the potential mechanism of candidate genes participating in OSAHS by bioinformatics analysis. Fifty cases of severe OSAHS and 50 cases of non-OSAHS were selected from the Xinjiang Uygur Municipal Peoples Hospital for second-generation sequencing of the target region to screen out the susceptibility loci of OSAHS, and establish a weighted genetic risk score(GRS) to analyze its correlation with OSAHS. The predictive effect of interaction between GRS and traditional factors on OSAHS was analyzed. Results Bioinformatics analysis indicated that 44 candidate genes were involved in biological processes and signal pathways related to sleep and circadian rhythm. Logistic regression analysis was carried out for the variation under different genetic models. After adjusting for potential confounding factors, it was found that KSR2, NPAS2, OXTR and GHRL genes were significantly correlated with OSAHS. Six loci〖JP2〗(KSR2-rs2592290, rs1992750, rs66837180, NPAS2-rs22787727, OXTR-rs3806675 and GHRL-rs10490816) of the four genes were analyzed using GRS. The high GRS group had a higher risk of OSAHS than the low GRS group(OR=2.901, 95%CI: 1.288-6.534, P=0.010). After adding GRS to the regression model composed of traditional risk factors(age, sex and BMI) of OSAHS, the area under the curve(AUC) value increased from 0.877 to 0.902. Conclusion The sleep and circadian rhythm-related genes such as KSR2,NPAS2, OXTR and GHRL may be the genetic susceptibility genes for OSAHS. The combination of GRS established based on the six loci of the four genes and traditional factors could improve the prediction model of OSAHS.