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Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

Author

Listed:
  • Gyda Bjornsdottir

    (deCODE Genetics/Amgen, Inc.)

  • Lilja Stefansdottir

    (deCODE Genetics/Amgen, Inc.)

  • Gudmar Thorleifsson

    (deCODE Genetics/Amgen, Inc.)

  • Patrick Sulem

    (deCODE Genetics/Amgen, Inc.)

  • Kristjan Norland

    (deCODE Genetics/Amgen, Inc.)

  • Egil Ferkingstad

    (deCODE Genetics/Amgen, Inc.)

  • Asmundur Oddsson

    (deCODE Genetics/Amgen, Inc.)

  • Florian Zink

    (deCODE Genetics/Amgen, Inc.)

  • Sigrun H. Lund

    (deCODE Genetics/Amgen, Inc.)

  • Muhammad S. Nawaz

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

  • G. Bragi Walters

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

  • Astros Th. Skuladottir

    (deCODE Genetics/Amgen, Inc.)

  • Sigurjon A. Gudjonsson

    (deCODE Genetics/Amgen, Inc.)

  • Gudmundur Einarsson

    (deCODE Genetics/Amgen, Inc.)

  • Gisli H. Halldorsson

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

  • Valgerdur Bjarnadottir

    (Landspitali University Hospital)

  • Gardar Sveinbjornsson

    (deCODE Genetics/Amgen, Inc.)

  • Anna Helgadottir

    (deCODE Genetics/Amgen, Inc.)

  • Unnur Styrkarsdottir

    (deCODE Genetics/Amgen, Inc.)

  • Larus J. Gudmundsson

    (deCODE Genetics/Amgen, Inc.)

  • Ole B. Pedersen

    (Zealand University Hospital
    University of Copenhagen)

  • Thomas Folkmann Hansen

    (Rigshospitalet-Glostrup
    University of Copenhagen)

  • Thomas Werge

    (University of Copenhagen
    Copenhagen University Hospital
    University of Copenhagen)

  • Karina Banasik

    (University of Copenhagen)

  • Anders Troelsen

    (University of Copenhagen
    Copenhagen University Hospital)

  • Soren T. Skou

    (University of Southern Denmark
    Næstved-Slagelse-Ringsted Hospitals)

  • Lise Wegner Thørner

    (Copenhagen University Hospital)

  • Christian Erikstrup

    (Aarhus University Hospital)

  • Kaspar Rene Nielsen

    (Aalborg University Hospital)

  • Susan Mikkelsen

    (Aarhus University Hospital)

  • Ingileif Jonsdottir

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

  • Aron Bjornsson

    (Landspitali University Hospital)

  • Ingvar H. Olafsson

    (Landspitali University Hospital)

  • Elfar Ulfarsson

    (Landspitali University Hospital)

  • Josep Blondal

    (Health Care Institution of West Iceland)

  • Arnor Vikingsson

    (Landspitali University Hospital)

  • Soren Brunak

    (University of Copenhagen)

  • Sisse R. Ostrowski

    (University of Copenhagen
    Copenhagen University Hospital)

  • Henrik Ullum

    (Statens Serum Institut, Copenhagen)

  • Unnur Thorsteinsdottir

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

  • Hreinn Stefansson

    (deCODE Genetics/Amgen, Inc.)

  • Daniel F. Gudbjartsson

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

  • Thorgeir E. Thorgeirsson

    (deCODE Genetics/Amgen, Inc.)

  • Kari Stefansson

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

Abstract

Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.

Suggested Citation

  • Gyda Bjornsdottir & Lilja Stefansdottir & Gudmar Thorleifsson & Patrick Sulem & Kristjan Norland & Egil Ferkingstad & Asmundur Oddsson & Florian Zink & Sigrun H. Lund & Muhammad S. Nawaz & G. Bragi Wa, 2022. "Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28167-1
    DOI: 10.1038/s41467-022-28167-1
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