Association of genetic risk score and chronic kidney disease in a Japanese population

Nephrology (Carlton). 2019 Jun;24(6):670-673. doi: 10.1111/nep.13479. Epub 2019 Apr 29.

Abstract

Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies have discovered CKD susceptibility variants. We developed a genetic risk score (GRS) based on CKD-associated variants and assessed a possibility that the GRS can improve the discrimination capability for the prevalence of CKD in a Japanese population. The present study consists of 11 283 participants randomly selected from 12 Japan Multi-Institutional Collaborative Cohort Study sites. Individual GRS was constructed combining 18 single-nucleotide polymorphisms identified in a Japanese population. Participants with eGFR <60 mL/min per 1.73 m2 was defined as case (stage 3 CKD or higher) in this study. Logistic regression analysis was used to examine the association between the GRS and CKD risk with adjustment for sex, age, hypertension and type 2 diabetes mellitus. The frequency of individuals with CKD was 8.3%, which was relatively low compared with those previously reported in a Japanese population. The odds ratio of having CKD was 1.120 (95% confidence interval: 1.042-1.203) per 10 GRS increment in the fully adjusted model (P = 0.002). The C-statistic was significantly increased in the model with the GRS, comparing with the model without the GRS (0.720 vs 0.719, Pdifference = 0.008). Increment of the GRS was associated with increased risk of CKD. Additionally, the GRS significantly improved the discriminatory ability of CKD prevalence in a Japanese population; however, the improvement of discriminatory ability brought about by the GRS seemed to be small compared with that of non-genetic CKD risk factors.

Keywords: chronic kidney disease; estimated glomerular filtration rate; genetic epidemiology; genetic risk score.

Publication types

  • Multicenter Study

MeSH terms

  • Asian People / genetics*
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Molecular Epidemiology
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / ethnology
  • Renal Insufficiency, Chronic / genetics*
  • Risk Assessment
  • Risk Factors

Substances

  • Genetic Markers