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- URN zum Zitieren dieses Dokuments:
- urn:nbn:de:bvb:355-epub-528094
- DOI zum Zitieren dieses Dokuments:
- 10.5283/epub.52809
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Dokumentenart: | Artikel | ||||
---|---|---|---|---|---|
Open Access Art: | Hybrid Open Acces | ||||
Titel eines Journals oder einer Zeitschrift: | Kidney International | ||||
Verlag: | Elsevier | ||||
Ort der Veröffentlichung: | NEW YORK | ||||
Band: | 102 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 3 | ||||
Seitenbereich: | S. 624-639 | ||||
Datum: | 16 Juni 2022 | ||||
Institutionen: | Medizin > Abteilung für Nephrologie Medizin > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medizin > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | CLINICAL-PRACTICE; BASE-LINE; DISEASE; PROGRESSION; SHROOM3; ADJUSTMENT; VARIANTS; EXAMPLE; RISK; BIAS; acute kidney injury; chronic kidney disease; diabetes; gene expression | ||||
Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 52809 |
Zusammenfassung
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 ...
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Zusammenfassung
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.
Metadaten zuletzt geändert: 14 Dez 2022 14:45