IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-07460-y.html
   My bibliography  Save this article

Genome-wide association meta-analysis yields 20 loci associated with gallstone disease

Author

Listed:
  • Egil Ferkingstad

    (deCODE Genetics/Amgen, Inc.)

  • Asmundur Oddsson

    (deCODE Genetics/Amgen, Inc.)

  • Solveig Gretarsdottir

    (deCODE Genetics/Amgen, Inc.)

  • Stefania Benonisdottir

    (deCODE Genetics/Amgen, Inc.)

  • Gudmar Thorleifsson

    (deCODE Genetics/Amgen, Inc.)

  • Aimee M. Deaton

    (deCODE Genetics/Amgen, Inc.)

  • Stefan Jonsson

    (deCODE Genetics/Amgen, Inc.)

  • Olafur A. Stefansson

    (deCODE Genetics/Amgen, Inc.)

  • Gudmundur L. Norddahl

    (deCODE Genetics/Amgen, Inc.)

  • Florian Zink

    (deCODE Genetics/Amgen, Inc.)

  • Gudny A. Arnadottir

    (deCODE Genetics/Amgen, Inc.)

  • Bjarni Gunnarsson

    (deCODE Genetics/Amgen, Inc.)

  • Gisli H. Halldorsson

    (deCODE Genetics/Amgen, Inc.)

  • Anna Helgadottir

    (deCODE Genetics/Amgen, Inc.)

  • Brynjar O. Jensson

    (deCODE Genetics/Amgen, Inc.)

  • Ragnar P. Kristjansson

    (deCODE Genetics/Amgen, Inc.)

  • Gardar Sveinbjornsson

    (deCODE Genetics/Amgen, Inc.)

  • David A. Sverrisson

    (deCODE Genetics/Amgen, Inc.)

  • Gisli Masson

    (deCODE Genetics/Amgen, Inc.)

  • Isleifur Olafsson

    (Landspítali University Hospital)

  • Gudmundur I. Eyjolfsson

    (Laboratory in Mjódd (RAM))

  • Olof Sigurdardottir

    (Akureyri Hospital)

  • Hilma Holm

    (deCODE Genetics/Amgen, Inc.)

  • Ingileif Jonsdottir

    (deCODE Genetics/Amgen, Inc.
    University of Iceland
    Landspitali University Hospital)

  • Sigurdur Olafsson

    (Landspitali University Hospital)

  • Thora Steingrimsdottir

    (University of Iceland
    Landspitali University Hospital)

  • Thorunn Rafnar

    (deCODE Genetics/Amgen, Inc.)

  • Einar S. Bjornsson

    (University of Iceland
    Landspitali University Hospital)

  • Unnur Thorsteinsdottir

    (deCODE Genetics/Amgen, Inc.
    University of Iceland)

  • Daniel F. Gudbjartsson

    (deCODE Genetics/Amgen, Inc.
    University of Iceland)

  • Patrick Sulem

    (deCODE Genetics/Amgen, Inc.)

  • Kari Stefansson

    (deCODE Genetics/Amgen, Inc.
    University of Iceland)

Abstract

Gallstones are responsible for one of the most common diseases in the Western world and are commonly treated with cholecystectomy. We perform a meta-analysis of two genome-wide association studies of gallstone disease in Iceland and the UK, totaling 27,174 cases and 736,838 controls, uncovering 21 novel gallstone-associated variants at 20 loci. Two distinct low frequency missense variants in SLC10A2, encoding the apical sodium-dependent bile acid transporter (ASBT), associate with an increased risk of gallstone disease (Pro290Ser: OR = 1.36 [1.25–1.49], P = 2.1 × 10–12, MAF = 1%; Val98Ile: OR = 1.15 [1.10–1.20], P = 1.8 × 10–10, MAF = 4%). We demonstrate that lower bile acid transport by ASBT is accompanied by greater risk of gallstone disease and highlight the role of the intestinal compartment of the enterohepatic circulation of bile acids in gallstone disease susceptibility. Additionally, two low frequency missense variants in SERPINA1 and HNF4A and 17 common variants represent novel associations with gallstone disease.

Suggested Citation

  • Egil Ferkingstad & Asmundur Oddsson & Solveig Gretarsdottir & Stefania Benonisdottir & Gudmar Thorleifsson & Aimee M. Deaton & Stefan Jonsson & Olafur A. Stefansson & Gudmundur L. Norddahl & Florian Z, 2018. "Genome-wide association meta-analysis yields 20 loci associated with gallstone disease," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07460-y
    DOI: 10.1038/s41467-018-07460-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-07460-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-07460-y?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Peter H. Dixon & Adam P. Levine & Inês Cebola & Melanie M. Y. Chan & Aliya S. Amin & Anshul Aich & Monika Mozere & Hannah Maude & Alice L. Mitchell & Jun Zhang & Jenny Chambers & Argyro Syngelaki & Je, 2022. "GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Sébastien Thériault & Zhonglin Li & Erik Abner & Jian’an Luan & Hasanga D. Manikpurage & Ursula Houessou & Pardis Zamani & Mewen Briend & Dominique K. Boudreau & Nathalie Gaudreault & Lily Frenette & , 2024. "Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    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_s41467-018-07460-y. 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.