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Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals

Author

Listed:
  • Kira J. Stanzick

    (University of Regensburg)

  • Yong Li

    (Faculty of Medicine and Medical Center–University of Freiburg)

  • Pascal Schlosser

    (Faculty of Medicine and Medical Center–University of Freiburg)

  • Mathias Gorski

    (University of Regensburg)

  • Matthias Wuttke

    (Faculty of Medicine and Medical Center–University of Freiburg)

  • Laurent F. Thomas

    (Norwegian University of Science and Technology
    Norwegian University of Science and Technology
    Norwegian University of Science and Technology)

  • Humaira Rasheed

    (Norwegian University of Science and Technology
    University of Bristol)

  • Bryce X. Rowan

    (Vanderbilt University Medical Center
    Tennessee Valley Healthcare System (626)/Vanderbilt University)

  • Sarah E. Graham

    (University of Michigan)

  • Brett R. Vanderweff

    (University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Snehal B. Patil

    (University of Michigan School of Public Health
    University of Michigan School of Public Health
    University of Michigan)

  • Cassiane Robinson-Cohen

    (Tennessee Valley Healthcare System (626)/Vanderbilt University
    and Vanderbilt Precision Nephrology Program Nashville)

  • John M. Gaziano

    (VA Boston Healthcare System
    Harvard Medical School)

  • Christopher J. O’Donnell

    (VA Boston Healthcare System)

  • Cristen J. Willer

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Stein Hallan

    (Norwegian University of Science and Technology
    Trondheim University Hospital)

  • Bjørn Olav Åsvold

    (Norwegian University of Science and Technology
    Trondheim University Hospital)

  • Andre Gessner

    (University Hospital Regensburg)

  • Adriana M. Hung

    (Tennessee Valley Healthcare System (626)/Vanderbilt University
    and Vanderbilt Precision Nephrology Program Nashville)

  • Cristian Pattaro

    (Institute for Biomedicine (affiliated with the University of Lübeck))

  • Anna Köttgen

    (Faculty of Medicine and Medical Center–University of Freiburg
    Johns Hopkins Bloomberg School of Public Health)

  • Klaus J. Stark

    (University of Regensburg)

  • Iris M. Heid

    (University of Regensburg)

  • Thomas W. Winkler

    (University of Regensburg)

Abstract

Genes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n = 1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n = 1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, ≤5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n = 460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24491-0
    DOI: 10.1038/s41467-021-24491-0
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    Cited by:

    1. Matthias Wuttke & Eva König & Maria-Alexandra Katsara & Holger Kirsten & Saeed Khomeijani Farahani & Alexander Teumer & Yong Li & Martin Lang & Burulca Göcmen & Cristian Pattaro & Dorothee Günzel & An, 2023. "Imputation-powered whole-exome analysis identifies genes associated with kidney function and disease in the UK Biobank," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Danielle Rasooly & Gina M. Peloso & Alexandre C. Pereira & Hesam Dashti & Claudia Giambartolomei & Eleanor Wheeler & Nay Aung & Brian R. Ferolito & Maik Pietzner & Eric H. Farber-Eger & Quinn Stanton , 2023. "Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Markus Scholz & Katrin Horn & Janne Pott & Matthias Wuttke & Andreas Kühnapfel & M. Kamal Nasr & Holger Kirsten & Yong Li & Anselm Hoppmann & Mathias Gorski & Sahar Ghasemi & Man Li & Adrienne Tin & J, 2024. "X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response element," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Ruth F. Dubin & Rajat Deo & Yue Ren & Jianqiao Wang & Zihe Zheng & Haochang Shou & Alan S. Go & Afshin Parsa & James P. Lash & Mahboob Rahman & Chi-yuan Hsu & Matthew R. Weir & Jing Chen & Amanda Ande, 2023. "Proteomics of CKD progression in the chronic renal insufficiency cohort," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Kelly Yichen Li & Claudia Ha Ting Tam & Hongbo Liu & Samantha Day & Cadmon King Poo Lim & Wing Yee So & Chuiguo Huang & Guozhi Jiang & Mai Shi & Heung Man Lee & Hui-yao Lan & Cheuk-Chun Szeto & Robert, 2023. "DNA methylation markers for kidney function and progression of diabetic kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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