Abstract

Background

The factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline.

Methods

We analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3–5-year observation period. eGFR decline was defined in separate analyses as “clinical” (> -1.0 ml/min/1.73 m2/year) or “empirical” (lower most quartile of eGFR slopes).

Results

The mean baseline eGFR was ~ 86 ml/min/1.73 m2. Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD.

Conclusion

Common genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens.

Details

Title
Polygenic association of glomerular filtration rate decline in world trade center responders
Author
Koraishy, Farrukh M; Mann, Frank D; Waszczuk, Monika A; Kuan, Pei-Fen; Jonas, Katherine; Yang, Xiaohua; Docherty, Anna; Shabalin, Andrey; Clouston, Sean; Kotov, Roman; Luft, Benjamin
Pages
1-10
Section
Research
Publication year
2022
Publication date
2022
Publisher
BioMed Central
e-ISSN
14712369
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2737783456
Copyright
© 2022. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.