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Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis

Author

Listed:
  • Harriet Corvol

    (Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Trousseau
    Institut National de la Santé et la Recherche Médicale (INSERM) U938
    Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06)

  • Scott M. Blackman

    (Johns Hopkins University School of Medicine)

  • Pierre-Yves Boëlle

    (Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06
    AP-HP, Hôpital St Antoine)

  • Paul J. Gallins

    (University of North Carolina at Chapel Hill)

  • Rhonda G. Pace

    (Marsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill)

  • Jaclyn R. Stonebraker

    (Marsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill)

  • Frank J. Accurso

    (Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Center
    Children’s Hospital Colorado, Anschutz Medical Center
    School of Medicine, Anschutz Medical Center)

  • Annick Clement

    (Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Trousseau
    Institut National de la Santé et la Recherche Médicale (INSERM) U938
    Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06)

  • Joseph M. Collaco

    (Johns Hopkins University School of Medicine)

  • Hong Dang

    (Marsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill)

  • Anthony T. Dang

    (Marsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill)

  • Arianna Franca

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine)

  • Jiafen Gong

    (Program in Genetics and Genome Biology, The Hospital for Sick Children)

  • Loic Guillot

    (Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Trousseau
    Institut National de la Santé et la Recherche Médicale (INSERM) U938)

  • Katherine Keenan

    (Program in Physiology and Experimental Medicine, The Hospital for Sick Children)

  • Weili Li

    (Program in Genetics and Genome Biology, The Hospital for Sick Children)

  • Fan Lin

    (Program in Genetics and Genome Biology, The Hospital for Sick Children)

  • Michael V. Patrone

    (Marsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill)

  • Karen S. Raraigh

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine)

  • Lei Sun

    (University of Toronto
    Dalla Lana School of Public Health, University of Toronto)

  • Yi-Hui Zhou

    (North Carolina State University)

  • Wanda K. O’Neal

    (Marsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill)

  • Marci K. Sontag

    (Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Center
    Children’s Hospital Colorado, Anschutz Medical Center
    School of Medicine, Anschutz Medical Center)

  • Hara Levy

    (Stanley Manne Research Institute, Northwestern University Feinberg School of Medicine, Ann and Robert Lurie Children’s Hospital of Chicago)

  • Peter R. Durie

    (Program in Physiology and Experimental Medicine, The Hospital for Sick Children
    University of Toronto)

  • Johanna M. Rommens

    (Program in Genetics and Genome Biology, The Hospital for Sick Children
    University of Toronto)

  • Mitchell L. Drumm

    (School of Medicine, Case Western Reserve University)

  • Fred A. Wright

    (North Carolina State University
    North Carolina State University)

  • Lisa J. Strug

    (Program in Genetics and Genome Biology, The Hospital for Sick Children
    Dalla Lana School of Public Health, University of Toronto)

  • Garry R. Cutting

    (McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Michael R. Knowles

    (Marsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill)

Abstract

The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10−11), chr5p15.3 (SLC9A3; P=6.8 × 10−12), chr6p21.3 (HLA Class II; P=1.2 × 10−8) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10−9) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10−10), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.

Suggested Citation

  • Harriet Corvol & Scott M. Blackman & Pierre-Yves Boëlle & Paul J. Gallins & Rhonda G. Pace & Jaclyn R. Stonebraker & Frank J. Accurso & Annick Clement & Joseph M. Collaco & Hong Dang & Anthony T. Dang, 2015. "Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis," Nature Communications, Nature, vol. 6(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9382
    DOI: 10.1038/ncomms9382
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    Cited by:

    1. Lin Zhang & Lei Sun, 2022. "A generalized robust allele‐based genetic association test," Biometrics, The International Biometric Society, vol. 78(2), pages 487-498, June.

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