Association between polygenic risk scores for hypertension and low-density lipoprotein cholesterol with incident chronic kidney disease.

Background: The clinical implications of genetic risk for hypertension (HTN) and high low-density lipoprotein cholesterol (LDL-C) levels in incident chronic kidney disease (CKD) are unknown. This study aimed to examine whether polygenic risk scores (PRSs) for these two factors can predict the development of CKD.

Methods: We included 245,893 participants enrolled in UK Biobank during 2006-2010 and followed up until 2022. The primary exposures were the PRS for HTN (PRS HTN) and high LDL-C concentration (PRS LDL-C). The primary outcome was incident CKD, assessed using cause-specific competing-risk models.

Results: During a median follow-up of 13.7 years (interquartile range, 13.0-14.3 years), 7,771 individuals experienced CKD. A 1-standard deviation higher PRS HTN was associated with a 7% higher risk of incident CKD (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.05-1.10). However, PRS LDL-C showed no significant association with incident CKD. In a combined association analysis based on the four groups classified by the median values of PRS, the HRs were 1.03 (95% CI, 0.97-1.10) in the high LDL-C-risk group and 1.13 (95% CI, 1.06-1.20) in both the high HTN group and the combined high-risk group, compared with the reference group.

Conclusion: This study showed that individuals with a higher genetic predisposition to HTN were more likely to develop CKD than those predisposed to a high LDL-C concentration. Additionally, higher genetic predispositions for these two factors did not synergically contribute to the risk of CKD.