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논문분류	춘계학술대회 초록집
제목	Integrated genomics and metabolomics to identify cause-specific biomarkers for chronic kidney disease in Korean population
저자	Min Woo Kang
출판정보	2024; 2024(1):
키워드
초록	Objectives: The heterogeneity of chronic kidney disease (CKD) features and the fragmentary nature of analysis methods may impede the precise identification of novel biomarkers. Herein, we addressed this issue by utilizing two independent cohorts to integrate genomics and metabolomics, aiming to identify cause-specific biomarkers for CKD and its progression in Korean population. Methods: A longitudinal genome-wide survival analysis was conducted using the Ansan and Ansung cohort (n=5,194), a part of Korean Genome and Epidemiology Study. To validate these genomic biomarkers and integrate them with metabolomic biomarker, we used a biopsy-confirmed CKD cohort from Seoul National University Hospital in Korea. In this cohort, we analyzed 4 disease groups matched for age and sex, namely type 2 diabetic kidney disease (DKD) (n=64), hypertensive nephropathy (HN) (n=24), immunoglobulin A nephropathy (IgAN) (n=66), and membranous nephropathy (MN) (n=66), and compared them with healthy individuals (n=66). In the biopsy cohort, significant SNPs and metabolites for each CKD subset were identified, and cause-specific biomarker pairs were selected using correlation-based network analysis. Subsequently, the risk of kidney progression associated with the identified pairs was assessed. Results: From the Ansan and Ansung cohort, we analyzed 451,172 SNP variants, identifying a total of 448 variants significant for CKD development. Among these, 11, 10, 13, and 21 variants were selected as significant in DKD, HN, IgAN, and MN, respectively, in the biopsy cohort. Regarding plasma metabolomics, 51, 28, 29, and 71 metabolites in DKD, HN, IgAN, and MN, respectively, were identified. Accordingly, we identified 36 pairs of SNP variants and metabolites, and 5 pairs exhibited an association with only one specific disease subset. Within these pairs, the rs1025170 and tyrosine pair correlated with the progression of DKD. Conclusions: Integrating both genomics and metabolomics with independent cohorts enables the discovery of cause-specific biomarkers for CKD and its progression in Korean population.
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