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Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation

Author

Listed:
  • Gyda Bjornsdottir

    (deCODE Genetics/Amgen, Inc.)

  • Stefania Benonisdottir

    (deCODE Genetics/Amgen, Inc.)

  • Gardar Sveinbjornsson

    (deCODE Genetics/Amgen, Inc.)

  • Unnur Styrkarsdottir

    (deCODE Genetics/Amgen, Inc.)

  • Gudmar Thorleifsson

    (deCODE Genetics/Amgen, Inc.)

  • G. Bragi Walters

    (deCODE Genetics/Amgen, Inc.)

  • Aron Bjornsson

    (Landspitali University Hospital)

  • Ingvar H. Olafsson

    (Landspitali University Hospital
    Faculty of Medicine, University of Iceland)

  • Elfar Ulfarsson

    (Landspitali University Hospital)

  • Arnor Vikingsson

    (Landspitali, National University Hospital
    Thraut Fibromyalgia Clinic)

  • Ragnheidur Hansdottir

    (University of Iceland)

  • Karl O. Karlsson

    (University of Iceland)

  • Thorunn Rafnar

    (deCODE Genetics/Amgen, Inc.)

  • Ingileif Jonsdottir

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

  • Michael L. Frigge

    (deCODE Genetics/Amgen, Inc.)

  • Augustine Kong

    (deCODE Genetics/Amgen, Inc.
    School of Engineering and Natural Sciences, Science Institute, University of Iceland)

  • Asmundur Oddsson

    (deCODE Genetics/Amgen, Inc.)

  • Gisli Masson

    (deCODE Genetics/Amgen, Inc.)

  • Olafur T. Magnusson

    (deCODE Genetics/Amgen, Inc.)

  • Tomas Gudbjartsson

    (Faculty of Medicine, University of Iceland
    Landspitali University Hospital)

  • Hreinn Stefansson

    (deCODE Genetics/Amgen, Inc.)

  • Patrick Sulem

    (deCODE Genetics/Amgen, Inc.)

  • Daniel Gudbjartsson

    (deCODE Genetics/Amgen, Inc.
    School of Engineering and Natural Sciences, Science Institute, University of Iceland)

  • Unnur Thorsteinsdottir

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

  • Thorgeir E. Thorgeirsson

    (deCODE Genetics/Amgen, Inc.)

  • Kari Stefansson

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

Abstract

Lumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10−12) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height. In light of presented findings, we speculate that the effect of rs6651255 on LDHsurg is driven by susceptibility to developing severe and persistent sciatica upon LDH.

Suggested Citation

  • Gyda Bjornsdottir & Stefania Benonisdottir & Gardar Sveinbjornsson & Unnur Styrkarsdottir & Gudmar Thorleifsson & G. Bragi Walters & Aron Bjornsson & Ingvar H. Olafsson & Elfar Ulfarsson & Arnor Vikin, 2017. "Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation," Nature Communications, Nature, vol. 8(1), pages 1-8, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14265
    DOI: 10.1038/ncomms14265
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    Cited by:

    1. Ville Salo & Juhani Määttä & Eeva Sliz & Ene Reimann & Reedik Mägi & Kadri Reis & Abdelrahman G. Elhanas & Anu Reigo & Priit Palta & Tõnu Esko & Jaro Karppinen & Johannes Kettunen, 2024. "Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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