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Abstract: FR-PO304

Polygenic Risk Score for CKD: Association Between Dyslipidemia and the Risk of Incident CKD Affected by Genetic Susceptibility

Session Information

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Weon, Boram, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
  • Lee, Jeonghwan, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
  • Lee, Jung Pyo, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
  • Lim, Chun Soo, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
Background

Polygenic risk score (PRS) provides information of the overall contribution of numerous genetic variants on disease outcomes. The effect of dyslipidemia on kidney disease outcome are inconsistent according to the individual’s clinical characteristics including eGFR and genetic background. We aimed to investigate the genetic effect on the association between dyslipidemia and risk of CKD using PRS.

Methods

We constructed PRS for incident CKD using GWAS summary statistics of CKDGen Overall European Ancestry (n=480,898). UK biobank participants (aged 40 to 69) registered between 2006 and 2010 were enrolled in this study (n=389,281). Incident CKD was defined as eGFR below 60 ml/min/1.73 m2 and ICD-10 code of CKD during follow-up period. The effect of lipid profile [total cholesterol (Total-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglyceride(TG)] and PRS on incident CKD was investigated using the Cox proportional hazard model. Multivariable analysis included age, sex, comorbidities (diabetes mellitus and hypertension), body mass index, baseline kidney function, proteinuria, uric acid levels, alcohol consumption, and smoking as covariates. Interactions between lipid profile and PRS were tested in the whole participants and subgroups stratified by PRS for incidenet CKD.

Results

A total of 4,890 (1.24%) of participants developed CKD. High PRS (HR 1.117, 95% CI 1.086-1.1.49 as continuous variable) was associated with increased risk of CKD in univariable analysis. In multivariable analysis, high TG (HR 1.097, 95% CI 1.069-1.125), low HDL-C (HR 0.606, 95% CI 0.545-0.674), low LDL-C (HR 0.838, 95% CI 0.806-0.871), and low total-C (HR 0.866, 95% CI 0.841-0.892) were associated with incident CKD. High PRS (HR 1.173, 95% CI 1.107-1.243) was associated with CKD only in conjunction with TG. There were positive interaction between PRS and lipid profile of total-C (HR 1.030, 95% CI 1.006-1.055) and HDL-C (HR 1.138, 95% CI 1.044-1.242). When stratified by PRS tertiles, significant interaction was discovered only in high PRS group.

Conclusion

PRS can significantly predict the risk of incident CKD. High TG and low HDL-C are associated with increased risk of CKD. Low LDL-C and TG are also associated with high incidence of CKD, and their effect on CKD tends to increase as the genetic risk of CKD increases.