IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-03646-6.html
   My bibliography  Save this article

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Author

Listed:
  • Adriana I. Iglesias

    (Erasmus Medical Center
    Erasmus Medical Center
    Erasmus Medical Center)

  • Aniket Mishra

    (Bordeaux Population Health Research Center)

  • Veronique Vitart

    (University of Edinburgh)

  • Yelena Bykhovskaya

    (Cedars-Sinai Medical Center
    Cornea Genetic Eye Institute)

  • René Höhn

    (University Medical Center Mainz
    University of Bern)

  • Henriët Springelkamp

    (Erasmus Medical Center)

  • Gabriel Cuellar-Partida

    (QIMR Berghofer Medical Research Institute)

  • Puya Gharahkhani

    (QIMR Berghofer Medical Research Institute)

  • Jessica N. Cooke Bailey

    (Case Western Reserve University
    Case Western Reserve University)

  • Colin E. Willoughby

    (Ulster University
    Belfast Health and Social Care Trust)

  • Xiaohui Li

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Seyhan Yazar

    (University of Edinburgh
    University of Western Australia, Lions Eye Institute)

  • Abhishek Nag

    (King’s College London)

  • Anthony P. Khawaja

    (University of Cambridge School of Clinical Medicine
    Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology)

  • Ozren Polašek

    (University of Split)

  • David Siscovick

    (University of Washington
    The New York Academy of Medicine)

  • Paul Mitchell

    (University of Sydney)

  • Yih Chung Tham

    (Singapore National Eye Centre)

  • Jonathan L. Haines

    (Case Western Reserve University
    Case Western Reserve University)

  • Lisa S. Kearns

    (Royal Victorian Eye and Ear Hospital)

  • Caroline Hayward

    (University of Edinburgh)

  • Yuan Shi

    (Singapore National Eye Centre)

  • Elisabeth M. Leeuwen

    (Erasmus Medical Center)

  • Kent D. Taylor

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Pieter Bonnemaijer

    (Erasmus Medical Center)

  • Jerome I. Rotter

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Nicholas G. Martin

    (QIMR Berghofer Medical Research Institute)

  • Tanja Zeller

    (University Heart Center Hamburg
    Partner Site Hamburg/Kiel/Lübeck)

  • Richard A. Mills

    (Flinders University)

  • Emmanuelle Souzeau

    (Flinders University)

  • Sandra E. Staffieri

    (Royal Victorian Eye and Ear Hospital)

  • Jost B. Jonas

    (Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg)

  • Irene Schmidtmann

    (University Medical Center Mainz)

  • Thibaud Boutin

    (University of Edinburgh)

  • Jae H. Kang

    (Brigham and Women’s Hospital)

  • Sionne E. M. Lucas

    (University of Tasmania)

  • Tien Yin Wong

    (Singapore National Eye Centre
    Duke-NUS Medical School
    National University of Singapore)

  • Manfred E. Beutel

    (University Medical Center Mainz)

  • James F. Wilson

    (University of Edinburgh
    University of Edinburgh)

  • André G. Uitterlinden

    (Erasmus Medical Center
    Erasmus Medical Center
    Netherlands Genomics Initiative)

  • Eranga N. Vithana

    (Singapore National Eye Centre)

  • Paul J. Foster

    (Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology)

  • Pirro G. Hysi

    (King’s College London)

  • Alex W. Hewitt

    (Royal Victorian Eye and Ear Hospital
    University of Tasmania)

  • Chiea Chuen Khor

    (Genome Institute of Singapore)

  • Louis R. Pasquale

    (Brigham and Women’s Hospital
    Harvard Medical School and Massachusetts Eye and Ear Infirmary)

  • Grant W. Montgomery

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

  • Caroline C. W. Klaver

    (Erasmus Medical Center
    Erasmus Medical Center
    Radboud University Medical Center)

  • Tin Aung

    (Singapore National Eye Centre
    Duke-NUS Medical School
    National University of Singapore)

  • Norbert Pfeiffer

    (University Medical Center Mainz)

  • David A. Mackey

    (University of Western Australia, Lions Eye Institute)

  • Christopher J. Hammond

    (King’s College London)

  • Ching-Yu Cheng

    (Singapore National Eye Centre
    Duke-NUS Medical School
    National University of Singapore)

  • Jamie E. Craig

    (Flinders University)

  • Yaron S. Rabinowitz

    (Cedars-Sinai Medical Center
    Cornea Genetic Eye Institute)

  • Janey L. Wiggs

    (Harvard Medical School and Massachusetts Eye and Ear Infirmary)

  • Kathryn P. Burdon

    (University of Tasmania)

  • Cornelia M. Duijn

    (Erasmus Medical Center)

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute)

Abstract

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = −0.62, P = 5.30 × 10−5) but not between CCT and primary open-angle glaucoma (r = −0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Suggested Citation

  • Adriana I. Iglesias & Aniket Mishra & Veronique Vitart & Yelena Bykhovskaya & René Höhn & Henriët Springelkamp & Gabriel Cuellar-Partida & Puya Gharahkhani & Jessica N. Cooke Bailey & Colin E. Willoug, 2018. "Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03646-6
    DOI: 10.1038/s41467-018-03646-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-03646-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-03646-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03646-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.