Evaluation of a genetic risk score based on creatinine-estimated glomerular filtration rate and its association with kidney outcomes

Background. Meta-analysis of cross-sectional genome-wide association studies (GWAS) on creatinine-estimated glomerular filtration rate (eGFR(crea)) identified 53 single-nucleotide polymorphisms (SNPs). These SNP effects can be aggregated into a genetic risk score (GRS) for chronic kidney disease (CKD). To assess its clinical utility, we examined associations with creatinine-estimated kidney outcomes, both cross-sectionally and longitudinally. Additionally, we examined associations with cystatin C-estimated kidney outcomes to verify that a GRS based on eGFR(crea )SNPs represents the genetics underlying kidney function. Methods. In the community-based Prevention of REnal and Vascular ENdstage Disease (PREVEND) study, we assessed eGFIt(crea) and eGFIt(cysc )at baseline and four follow-up examinations. The GRS comprised 53 SNPs for eGFR(crea) weighted for reported effect-sizes. We adjusted for baseline demographics and renal risk factors. Results. We included 3649 subjects (median age 49 years, 52% male, median follow-up 11 years, n 85 baseline CKD, n = 154 incident CKD). At baseline, a higher GRS associated with lower eGFR(cre)(a) [adjusted B [95% confidence interval (CI)] = -2.05 (-2.45 to - 1.65) mL/min/1.73 m(2), P