4 nuclear families which included 9 patients suffering from house dust mites allergic rhinitis (AR) were enrolled in present study. Whole -genome sequencing were employed to screen the possibly candidate variations which were susceptible to AR. 85 common variations shared in the study subjects and were reported to be related to allergic diseases previously were detected. Moreover, 108 low-frequency and rare variations were identified and some of them involved in antigen processing and presentation, endocytosis and phagosome pathways. Replications of the variations found through whole-genome sequencing were performed in 402 independent AR patients and healthy controls. We demonstrated 4 gene variations or region which have been proved to be associated with allergy, including rs204993 in PBX2, rs2228145 in IL6R, rs1128670 in MRPL18 and rs34874585 in IGHV1-3. In addition, we still discovered 5 novel AR gene variations and regions that involved rs2259816 in HNF1A, rs2298428 in YDJC, rs1128670 in MRPL18, rs2227983 in EGFR as well as rs1059091 in IFITM2.