Genome-wide polygenic risk score for estimated glomerular filtration slope predicts chronic kidney disease in a Taiwanese population.

Background: Kidney function decline is associated with cardiovascular disease and various other morbidities. Previous studies regarding polygenic risk scores of estimated glomerular filtration rate (eGFR) change were generally based on individuals of European ancestry and not validated on populations of East Asian ancestry.

Methods: We conducted a genome-wide association study for eGFR slope among 26,755 non-diabetic individuals from the Taiwan Biobank. We developed an eGFR slope polygenic risk score and validated its prediction power on chronic kidney disease (CKD) in another sample with 58,777 non-diabetic individuals.

Results: Eight candidate loci associated with eGFR slope (P-value ranging from 1.56 × 10^-6 to 8.73 × 10^-6) located in the SLC9A9, SLC26A8, DEPTOR, OBP2B, PRMT8, C19orf44 genes and an intergenic locus between MTMR12-ZFR genes were identified and a polygenic risk score for eGFR slope was constructed. The polygenic risk score was validated externally to be significantly associated with CKD in another set of individuals (P-value = 0.0182; odds ratio = 0.753; 95% confidence interval: 0.5936-0.9504).

Conclusions: We constructed a genome-wide polygenic risk score for eGFR decline and externally validated its use in predicting CKD in another Taiwan population. Our eGFR slope polygenic risk score might be useful for clinical CKD risk assessment in future, especially for East Asians.