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

Fujii R1, Hishida A2, Nakatochi M3, Furusyo N4, Murata M4, Tanaka K5, Shimanoe C5, Suzuki S6, Watanabe M6, Kuriyama N7, Koyama T7, Takezaki T8, Shimoshikiryo I8, Arisawa K9, Katsuura-Kamano S9, Takashima N10, Turin TC11, Kuriki K12, Endoh K12, Mikami H13, Nakamura Y13, Oze I14, Ito H14, Kubo M15, Momozawa Y15, Kondo T1, Naito M2, Wakai K2.

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Abstract

Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies (GWAS) 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 (J-MICC) Study sites. Individual GRS was constructed combining 18 single nucleotide polymorphisms (SNP) identified in a Japanese population. Participants with eGFR <60 mL/min/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. This article is protected by copyright. All rights reserved.