Genetic risk score raises the risk of incidence of chronic kidney disease in Korean general population-based cohort

Clin Exp Nephrol. 2019 Aug;23(8):995-1003. doi: 10.1007/s10157-019-01731-8. Epub 2019 Apr 6.

Abstract

Background: Chronic kidney disease (CKD) is a common disease, affecting about 10% of the general population. The genetic component about CKD incidence in Asian population is not well known. The aim of the study is to find the genetic loci associated with incident CKD and to figure out the effect of genetic variation on the development of CKD.

Methods: We conducted a genome-wide association (GWA) study regarding the development of CKD based on two population-based cohorts of Korean Genome Epidemiology Study. 3617 Koreans from two different cohorts, aged 40-49 years without CKD at initial visit, were included in our analysis. We used 2510 individuals in Ansan as the discovery set and another 1107 individuals from Ansung as the replication set. At baseline, members of both cohorts provided information on creatinine, and DNA samples were collected for genotyping. Single nucleotide polymorphisms that surpassed a significance threshold of P < 5 × 10-3 were selected.

Results: A total of 281 among 3617 developed CKD during the follow-up period. Incident CKD group was older (P < 0.001), included more female (P < 0.001), and had more hypertension and diabetes (P < 0.001). We identified 12 SNPs that are associated with incident CKD in the GWA study and made genetic risk score using these SNPs. In multiple Cox regression analysis, genetic risk score was still a significant associated factor (HR 1.311, CI 1.201, 1.431, P < 0.001).

Conclusions: We identified several loci highly associated with incident CKD. The findings suggest the need for further investigations on the genetic propensity for incident CKD.

Keywords: Chronic kidney disease; Genetic risk score; Genome-wide association study.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Asian People / genetics
  • Female
  • Gene Expression Profiling
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / ethnology
  • Renal Insufficiency, Chronic / genetics*
  • Republic of Korea / epidemiology
  • Risk Assessment
  • Risk Factors
  • Transcriptome*