Wiegrebe, S.* ; Gorski, M.* ; Herold, J.M.* ; Stark, K.J.* ; Thorand, B. ; Gieger, C. ; Böger, C.A.* ; Schödel, J.* ; Härtig, F.* ; Chen, H.* ; Winkler, T.W.* ; Küchenhoff, H.* ; Heid, I.M.*
Analyzing longitudinal trait trajectories using GWAS identifies genetic variants for kidney function decline.
Nat. Commun. 15:10061 (2024)
Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable for longGWAS. The linear mixed model identifies 13 independent genetic variants associated with eGFR-decline, including 6 novel variants, and links them to age-dependent eGFR-genetics. We demonstrate that age-dependent and age-independent eGFR-genetics exhibit a differential pattern regarding clinical progression traits and kidney-specific gene expression regulation. Overall, our results provide insights into kidney aging and linear mixed model-based longGWAS generally.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Genome-wide Association; Population; Health; Creatinine; Transport; Disease
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2024
Prepublished im Jahr
0
HGF-Berichtsjahr
2024
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 15,
Heft: 1,
Seiten: ,
Artikelnummer: 10061
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504000-002
G-504091-004
Förderungen
State of Bavaria
German Federal Ministry of Education and Research (BMBF)
Helmholtz Zentrum Muenchen-German Research Center for Environmental Health
UK Biobank resource
Deutsche Forschungsgemeinschaft (German Research Foundation)
Projekt DEAL
Copyright
Erfassungsdatum
2024-11-22