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. 2012 Jan;59(1):19-24.
doi: 10.1053/j.ajkd.2011.08.030. Epub 2011 Oct 13.

Performance of a genetic risk score for CKD stage 3 in the general population

Conall M O'Seaghdha  1 , Qiong Yang, Hongsheng Wu, Shih-Jen Hwang, Caroline S Fox
Affiliations

Performance of a genetic risk score for CKD stage 3 in the general population

Conall M O'Seaghdha et al. Am J Kidney Dis. 2012 Jan.

Abstract

Background: 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.

Study design: Observational cohort study.

Setting & 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).

Predictors: Single-nucleotide polymorphisms at 16 stage 3 CKD loci were genotyped and used to construct a genetic risk score. Standard clinical predictors of incident stage 3 CKD also were used.

Outcomes & measurements: Incident stage 3 CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) 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.

Results: There were 270 new stage 3 CKD cases during an average of 10.8 years of follow-up. Mean genetic risk score was 17.5 ± 2.8 (SD) for those who developed stage 3 CKD and 17.3 ± 2.6 for those who did not (P for genotype score difference = 0.2). The OR 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 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).

Limitations: All participants were of European ancestry; the genotype score may not be valid in different ancestral groups.

Conclusions: 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.

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Figures

Figure 1
Figure 1. Genotype Score Distribution among FHS Participants with and without stage 3 CKD
Figure shows distribution of participants according to genotype score, stratified according to persons in whom stage 3 CKD developed over the follow-up period (n = 270) and those in whom stage 3 CKD did not develop (n = 2219).
Figure 2
Figure 2. Comparison of receiver-operating characteristic curves for models with and without the genetic risk score and incident stage 3 CKD
Panel A is adjusted for age and sex; panel B is adjusted for standard CKD risk factors.
Figure 2
Figure 2. Comparison of receiver-operating characteristic curves for models with and without the genetic risk score and incident stage 3 CKD
Panel A is adjusted for age and sex; panel B is adjusted for standard CKD risk factors.
See this image and copyright information in PMC

Comment in

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