Abstract: Background：It is still unknown on the etiology, pathogenicity and associated prognostic factors of kawasaki disease(KD). Currently, multiple exposures which are collaborating with genetic background would induce the immunological responses and trigger the onset of KD, even coronary artery injuries. Objective：To explore the significance of genetic susceptibility related to KD, IVIG resistance and coronary artery lesions. Design：Casecontrol study. Methods：Complete KD was diagnosed according to American Heart Association(AHA) guidelines, and coronary artery lesion was defined with echocardiography Zscore>2 according to the JCS/JSCS 2020 guidelines. From April 2020 to January 2022, we continuously recruited complete KD patients at West China Second University Hospital of Sichuan University. The children who were underwent physical examination and blood test from child health department in our hospital were enrolled in the controls. The whole exome sequencing of peripheral blood samples, quality control of raw data, enrichment analysis and site annotation were performed to screen for single nucleotide polymorphisms (SNPs) and associated genes related to KD, IVIG resistance and coronary artery lesions, which helped to compare the response to treatment and clinical outcomes of KD. Main outcome measures：Sites of SNPs and genes which had been associated with KD, IVIG resistance and coronary artery lesions. Results：In total, 171 complete KD patients were enrolled, including 32 cases (27%) of coronary artery lesions and 55 cases (31%) of IVIG resistance, and 139 cases were enrolled in control group. There were no statistical differences in the age between two groups. A total of 609,732 SNPS were screened through upstream analysis. The two groups were separated by the principal component analysis categorized by Han and other ethic minorities, and there was no substructure in the principal component categorized by gender classification. With P<0.000 1 as the threshold, fifteen candidate genes were associated with KD susceptibility, including MYT1L、CYP26B1、NECTIN3、TENM3、GFI1B、KNDC1、LOC100133315、RNF121、SYNE3、MAPKBP1、SLFN14、MYOM1、ABCA7、PIP5K1C、PTGER1(30 SNPs). While six candidate genes had been identified to be associated with coronary artery lesion, including DGKH、CCDC130、KLF7、METTL6、COLQ、PRKN(19 SNPs). Moreover, there were also six candidate genes had been recognized as risk factors with IVIG resistance, including MICALCL、NT5DC3、KRT75、LOC105370980、TXK、BRD2(8 SNPs). Conclusion：In this study,MYT1L（chr2, rs4381806）、NECTIN3（chr3, rs2399373）、MAPKBP1（chr15, rs2303517）have some significance in exploring the pathogenesis of KD. The SNP sites and genes asscociated with IVIG resistance and coronary artery lesions required further investigation.

Key words: Kawasaki disease, Coronary artery lesion, Ggenome-wide association study, High-throughput sequencing, Bioinformatics