License: Creative Commons Attribution Non-commercial No Derivatives 4.0 PDF - Published Version (2MB) |
- URN to cite this document:
- urn:nbn:de:bvb:355-epub-528094
- DOI to cite this document:
- 10.5283/epub.52809
Item type: | Article | ||||
---|---|---|---|---|---|
Open Access Type: | Hybrid Open Acces | ||||
Journal or Publication Title: | Kidney International | ||||
Publisher: | Elsevier | ||||
Place of Publication: | NEW YORK | ||||
Volume: | 102 | ||||
Number of Issue or Book Chapter: | 3 | ||||
Page Range: | pp. 624-639 | ||||
Date: | 16 June 2022 | ||||
Institutions: | Medicine > Abteilung für Nephrologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie | ||||
Identification Number: |
| ||||
Keywords: | CLINICAL-PRACTICE; BASE-LINE; DISEASE; PROGRESSION; SHROOM3; ADJUSTMENT; VARIANTS; EXAMPLE; RISK; BIAS; acute kidney injury; chronic kidney disease; diabetes; gene expression | ||||
Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
Status: | Published | ||||
Refereed: | Yes, this version has been refereed | ||||
Created at the University of Regensburg: | Yes | ||||
Item ID: | 52809 |
Abstract
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for ...
Abstract
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics. Copyright (C) 2022, International Society of Nephrology. Published by Elsevier Inc.
Metadata last modified: 14 Dec 2022 14:45