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Analyzing longitudinal trait trajectories using GWAS identifies genetic variants for kidney function decline

Author

Listed:
  • Simon Wiegrebe

    (University of Regensburg
    LMU Munich)

  • Mathias Gorski

    (University of Regensburg)

  • Janina M. Herold

    (University of Regensburg)

  • Klaus J. Stark

    (University of Regensburg)

  • Barbara Thorand

    (Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH)
    German Center for Diabetes Research (DZD), Partner München-Neuherberg
    LMU Munich, Pettenkofer School of Public Health)

  • Christian Gieger

    (Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH)
    German Center for Diabetes Research (DZD), Partner München-Neuherberg
    Research Unit of Molecular Epidemiology, Helmholtz Zentrum München)

  • Carsten A. Böger

    (University Hospital Regensburg
    Traunstein Hospital, Southeast Bavarian Clinics
    KfH Kidney Centre Traunstein)

  • Johannes Schödel

    (Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Florian Hartig

    (University of Regensburg)

  • Han Chen

    (The University of Texas Health Science Center at Houston)

  • Thomas W. Winkler

    (University of Regensburg)

  • Helmut Küchenhoff

    (LMU Munich)

  • Iris M. Heid

    (University of Regensburg)

Abstract

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.

Suggested Citation

  • Simon Wiegrebe & Mathias Gorski & Janina M. Herold & Klaus J. Stark & Barbara Thorand & Christian Gieger & Carsten A. Böger & Johannes Schödel & Florian Hartig & Han Chen & Thomas W. Winkler & Helmut , 2024. "Analyzing longitudinal trait trajectories using GWAS identifies genetic variants for kidney function decline," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54483-9
    DOI: 10.1038/s41467-024-54483-9
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    References listed on IDEAS

    as
    1. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    2. Wenbo Tang & Matthew Kowgier & Daan W Loth & María Soler Artigas & Bonnie R Joubert & Emily Hodge & Sina A Gharib & Albert V Smith & Ingo Ruczinski & Vilmundur Gudnason & Rasika A Mathias & Tamara B H, 2014. "Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-13, July.
    3. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    4. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    5. B. Devlin & Kathryn Roeder, 1999. "Genomic Control for Association Studies," Biometrics, The International Biometric Society, vol. 55(4), pages 997-1004, December.
    6. R. A. Rigby & D. M. Stasinopoulos, 2005. "Generalized additive models for location, scale and shape," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 54(3), pages 507-554, June.
    7. Kira J. Stanzick & Yong Li & Pascal Schlosser & Mathias Gorski & Matthias Wuttke & Laurent F. Thomas & Humaira Rasheed & Bryce X. Rowan & Sarah E. Graham & Brett R. Vanderweff & Snehal B. Patil & Cass, 2021. "Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    8. Joshua D. Backman & Alexander H. Li & Anthony Marcketta & Dylan Sun & Joelle Mbatchou & Michael D. Kessler & Christian Benner & Daren Liu & Adam E. Locke & Suganthi Balasubramanian & Ashish Yadav & Ni, 2021. "Exome sequencing and analysis of 454,787 UK Biobank participants," Nature, Nature, vol. 599(7886), pages 628-634, November.
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