Yu Z, Jin J, Tin A, et al. - A polygenic risk score (PRS) for estimated glomerular filtration rate (eGFR) is now robust enough to capture risk for a wide range of incident kidney diseases and has a broad influence on the plasma proteome, mediated predominantly by eGFR.

• The authors created a genome-wide PRS for eGFR by applying the LDpred algorithm to summary statistics generated from a multiethnic meta-analysis of CKDGen Consortium Genome-wide association studies [GWAS] (N = 765,348) and UK Biobank GWAS (90% of the cohort; N = 451,508), followed by best parameter selection using the remaining 10% of UK Biobank (N = 45,158).

• The developing PRS exhibited substantial relationships with all outcomes, with hazard ratios ranging from 1.06 to 1.33 per 1 SD lower PRS.

• At both time points, the PRS was found to be strongly related to 132 proteins.

• Cystatin-C, collagen alpha-1(XV) chain, and desmocollin-2 had the strongest connections.

• Except for five proteins, including testican-2, most proteins were increased at poorer kidney function.

• The majority of the genetic PRS-protein correlations were mediated by eGFR.