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Association between polygenic risk scores for hypertension and low-density lipoprotein cholesterol with incident

Dong Hoon Kang1,2, Hyung Woo Kim1,3, Byoungwhi Ko1

  • 1Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.

Kidney Research and Clinical Practice
|June 26, 2025
PubMed

Insights

Genetic risk for hypertension (HTN) significantly increases chronic kidney disease (CKD) risk, while high LDL-C genetic risk does not. Combined genetic predispositions for HTN and high LDL-C do not synergistically elevate CKD risk.

Area of Science:

  • Genetics
  • Nephrology
  • Cardiovascular Disease

Background:

  • The clinical significance of genetic predisposition to hypertension (HTN) and high low-density lipoprotein cholesterol (LDL-C) for incident chronic kidney disease (CKD) remains unclear.
  • Investigating polygenic risk scores (PRSs) can elucidate these genetic associations.

Purpose of the Study:

  • To evaluate the predictive capability of PRSs for HTN and high LDL-C in the development of incident CKD.
  • To determine the independent and combined effects of genetic risk factors on CKD onset.

Main Methods:

  • Utilized UK Biobank data from 245,893 participants (2006-2022).
  • Assessed incident CKD using cause-specific competing-risk models.
  • Employed PRSs for HTN (PRS HTN) and high LDL-C (PRS LDL-C) as primary exposures.

Main Results:

  • A 1-SD increase in PRS HTN was linked to a 7% higher risk of incident CKD (HR, 1.07; 95% CI, 1.05-1.10).
  • PRS LDL-C showed no significant association with incident CKD.
  • Individuals in the high HTN genetic risk group exhibited a 13% increased CKD risk (HR, 1.13; 95% CI, 1.06-1.20).

Conclusions:

  • Higher genetic predisposition to HTN is associated with an increased risk of developing CKD.
  • Genetic risk for high LDL-C does not significantly predict CKD development.
  • Combined genetic predispositions for HTN and high LDL-C do not show synergistic effects on CKD risk.
Abstract

Keywords:
Chronic kidney diseaseDyslipidemiasHypertensionLow density lipoprotein cholesterolPolygenic risk score

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