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

Details

• Personal Author:
  Clouston S ; Docherty A ; Jonas K ; Koraishy FM ; Kotov R ; Kuan P-F ; Luft B ; Mann FD ; Shabalin A ; Waszczuk MA ; Yang X
• Description:
  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 approx. 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 (Beta = -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. [Description provided by NIOSH]
• Subjects:
  Blood Emergency Responders Hematologic Diseases Occupational Health Safety September 11 Terrorist Attacks
• Keywords:
  Author Keywords: Estimated Glomerular Fltration Rate Blood Sugar Disorders Chronic Kidney Disease CKD EGFR First Responders Kidney Disorders Kidneys Nephrological Disorders Polygenic Risk Score PRS Rescue Workers World Trade Center WTC

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• ISSN:
  1471-2369
• Document Type:
  Text
• Funding:
  Grant ; Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; New York ; OSHA Region 2 ; OSHA Region 5 ; OSHA Region 8 ; Utah
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  23
• Issue:
  1
• NIOSHTIC Number:
  nn:20066296
• Citation:
  BMC Nephrol 2022 Oct; 23(1):347
• Contact Point Address:
  Farrukh M. Koraishy, Division of Nephrology, Department of Medicine, Stony Brook University, 100 Nicolls Road, HSCT16-080E, Stony Brook, NY, USA
• Email:
  Farrukh.Koraishy@stonybrookmedicine.edu
• Federal Fiscal Year:
  2023
• Performing Organization:
  State University of New York Stony Brook
• Peer Reviewed:
  True
• Start Date:
  20210701
• Source Full Name:
  BMC Nephrology
• End Date:
  20230630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:db919589ddf90d7db6e3d55d251724e92eab4e4b058f48cb5b7b56948c6fd564cfc3e9adbc8154b5162e5c381ffda9dceeaacdba8d53c6c4a1833fbe867e68a1
• Download URL:
  https://stacks.cdc.gov/view/cdc/212772/cdc_212772_DS1.pdf
• File Type:
  [PDF - 1.24 MB ]