Genome-wide association of CKD progression: The chronic renal insufficiency cohort study

The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome-wide association study among participants in the Chronic Renal Insufficiency Cohort Study.Our outcome of interestwas CKD progression measured as change inEGFRover timeamong 1331blacks and 1476 whites with CKD.Westratified all analysesby race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P,1310^-6 for association with EGFR slope were selected as candidates for follow-up and secondarily tested for associationwith proteinuria and time to ESRD.Weidentified 12 such SNPsamong black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P=5.42310^-7; replication P=0.039; combined P=7.4231029). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P=4.9031026). Similarly, rs931891 in LINC00923 associated with EGFR decline (P=1.44310^-4) in white patients without diabetes. In summary, SNPs in LINC00923, an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.