Recent genome-wide association studies have identified multiple genetic loci that increase the risk of chronic kidney disease (CKD) in the general population. We hypothesized that knowledge of these loci might permit improved CKD risk prediction beyond that provided by traditional phenotypic risk factors.
Observational cohort study
Setting and participants
Participants who attended the 15th (1977–1979) and 24th (1995–1998) examination cycles of the Original cohort or the 6th (1995–1998) and 8th cycles (2005–2008) of the Offspring cohort of the Framingham Heart Study (n=2,489).
Single-nucleotide polymorphisms (SNPs) at 16 stage 3 CKD loci were genotyped and used to construct a genetic risk score. Standard clinical predictors of incident stage 3 CKD were also used.
Outcomes and Measurements
Incident stage 3 CKD was defined as eGFR <60 mL/min/1.73m2 at follow-up. Participants with baseline stage 3 CKD were excluded. Logistic regression was used to generate C statistics, which measured the power of the genetic risk score to discriminate risk of incident CKD stage 3 with and without traditional risk factors.
There were 270 new stage 3 CKD cases during an average of 10.8 years follow-up. The mean (±SD) genetic risk score was 17.5±2.8 among those who developed stage 3 CKD and 17.3±2.6 among those who did not (P-value for genotype score difference=0.2). The odds ratio for stage 3 CKD was 1.06 (95% CI, 1.01–1.11; p=0.03) per additional risk allele, adjusting for age and sex. In the age and sex-adjusted model, the C statistic was 0.748 without the genotype score and 0.751 with the score (P-value for difference=0.3). The risk score was not statistically significant in a multivariable model adjusted for standard stage 3 CKD risk factors (p=0.07).
Participants all of European ancestry; genotype score may not be valid in different ancestral groups.
A genetic score generated from 16 known CKD risk alleles did not predict new cases of stage 3 CKD in the community beyond knowledge of common, clinical risk factors alone.