Polygenic Association of Glomerular Filtration Rate Decline in World Trade Center Responders

Overview

Journal BMC Nephrol

Publisher Biomed Central

Specialty Nephrology

Date 2022 Oct 29

PMID 36307804

Authors

Farrukh M Koraishy

Frank D Mann

Monika A Waszczuk

Pei-Fen Kuan

Katherine Jonas

Xiaohua Yang

Anna Docherty

Andrey Shabalin

Sean Clouston

Roman Kotov

Benjamin Luft

Affiliations

Soon will be listed here.

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 m/year) or "empirical" (lower most quartile of eGFR slopes).

Results: The mean baseline eGFR was ~ 86 ml/min/1.73 m. 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.

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