Background: Genome-wide association studies (GWAS) of cystatin C have been conducted primarily in European countries, but studies in Asian populations are limited, so understanding the genetic predisposition and mechanisms of cystatin C in Koreans may provide new insights and therapeutic approaches for related conditions. Method: Using the Korean population-based cohorts HEXA and CAVAS, Lead SNPs with significance levels of p < 5E-08 in the meta-analysis were applied to the HEXA cohort to calculate a polygenic risk score (PRS). PRS was also used for a phenotype-wide association study (PheWAS) between 79 phenotypes. Functional gene analysis was conducted based on summary statistics from GWAS for the cystatin C levels at the meta-analysis using Multivariate Gene-Based Analysis of Genomic Annotation (MAGMA), the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) Results: The most statistically significant lead SNP was rs2897119 (intergenic, beta: -0.0393, SE: 0.0022, P: 2.89E-73). A 1 SD increase in standardized PRS was associated with an odds ratio of 1.21 (95% CI: 1.17-1.26) for developing chronic kidney disease (CKD). Gene-based analyses identified 17 genes associated with cystatin C levels. Gene set analysis identified IGF1R (P: 1.82E-12), which is involved in insulin binding, as being associated with SNPs in cystatin C. Conclusion: We identified 18 lead SNPs associated with cystatin C levels in the Korean population for the first time. The PRS and PheWAS results based on the lead SNPs showed that SNPs in cystatin C were associated with elevated cystatin C levels and risk of CKD. We also found an association between SNPs in cystatin C and IGF1R, which has been studied for kidney disease. This study may provide a genetic basis for SNPs and related genes of cystatin C levels in the Korean population. However, the sample size was smaller than in previous GWAS studies, so further research should be conducted.