Abstract: Objective Illumina next-generation sequencing technology combined with DNA pooling strategy and bioinformatics analysis were used to preliminarily screen the susceptibility genes for essential hypertension（EH） in the Dong population at whole genome level. Methods The study population consisted of 100 patients with EH and 100 healthy persons of Tongdao Dong. Extracted peripheral blood DNA and prepared two sets of DNA poolings. Two DNA libraries were constructed for genome resequencing with next-generation sequencing technologies. The sequencing data were compared with the reference genome using the comparison software BWA, and the obtained BAM comparison result were ready for analyzing single nucleotide polymorphism（SNP） and insertion-deletion（InDel） by GATK, for identifying copy number variations（CNV） by CNVnator, and structural variations（SV） by CNVnator Breakdancer. ANNOVAR and internal software AnnoDB were used to annotate the variants and variant impact. We obtained the significant（P＜0.05） possible disease-related SNPs in coding area between the EH and control group by Fisher exact test. Gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway were enriched by DAVID and KOBAS online tools for genes that differentially expressed. The protein-protein interaction network was constructed using the STRING database and we further selected the key susceptible EH-related genes and visualized resulting networks using the Cytoscape software. Results A total of 4 311 896 and 4 554 994 SNPs, 772 269 and 870 230 InDels, 8 027 and 7 052 CNVs, 5 534 and 8 072 SVs were identified in the normal control and EH group, respectively. These two groups shared 21 861 SNPs in coding area. Candidate gene screening was performed by using CytoNCA plugin in Cytoscape calculated each betweenness centrality（BC） and it was found more data flows through the portion of the differential expression of gene nodes including AKT serine/threonine kinase 1（AKT1）, epidermal growth factor receptor（EGFR）, angiotensin-converting enzyme（ACE）, integrin subunit beta 1（ITGB1）, matrix metalloproteinase 9（MMP9）, low density lipoprotein receptor（LDLR） and they had higher BC values than other genes. Conclusions Through the combination of DNA pooling and next-generation sequencing technology, a number of susceptibility genes that may be related to the occurrence and development of EH in the Tongdao Dong population were screened out. The signal pathway mediated with AKT1, EGFR and ACE may play important roles in the pathogenesis of EH in Tongdao Dong population.