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

  • Sohyun Yun
  • Miyeun Han
  • Hyo Jin Kim
  • Hyunsuk Kim
  • Eunjeong Kang
  • Sangsoo Kim
  • Curie Ahn
  • Kook-Hwan OhEmail author
Original article

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

Genome-wide association study Chronic kidney disease Genetic risk score 

Notes

Acknowledgements

Authors thank the National Biobank of Korea, the Centers for Disease Control and Prevention, Republic of Korea (4845-301, 4851-302 and -307) for sharing the bioresources. And this research was supported by the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2017M3A9E4044649).

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number KBP-2016-056) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was waived because the present study analyzed a deidentified dataset extracted from an established cohort study.

Supplementary material

10157_2019_1731_MOESM1_ESM.pdf (93 kb)
Additional file 1. Baseline characteristics between control and incident CKD group, dividing by gender (PDF 93 kb)
10157_2019_1731_MOESM2_ESM.tif (303 kb)
Additional file 2. A quantile plot of the observed p values (black dots) for the association of 1,590,162 SNPs (TIFF 302 kb)
10157_2019_1731_MOESM3_ESM.pdf (106 kb)
Additional file 3. Single nucleotide polymorphisms (SNPs) that showed the association with eGFR 30% reduction. (PDF 105 kb)

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Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  1. 1.Institute of Biomedical ResearchSeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Department of Internal MedicinePusan National University College of MedicineBusanRepublic of Korea
  3. 3.Department of Internal MedicineDongguk University College of MedicineGyeongju-SiRepublic of Korea
  4. 4.Department of Internal MedicineHallym University Medical Center, Chuncheon Sacred Heart HospitalChuncheon-SiRepublic of Korea
  5. 5.Department of Internal MedicineSeoul National University College of MedicineSeoulRepublic of Korea
  6. 6.Department of Bioinformatics and Life ScienceSoongsil UniversitySeoulRepublic of Korea

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