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

Gyda Bjornsdottir, Stefania Benonisdottir, Gardar Sveinbjornsson, Unnur Styrkarsdottir, Gudmar Thorleifsson, G. Bragi Walters, Aron Bjornsson, Ingvar H. Olafsson, Elfar Ulfarsson, Arnor Vikingsson, Ragnheidur Hansdottir, Karl O. Karlsson, Thorunn Rafnar, Ingileif Jonsdottir, Michael L. Frigge, Augustine Kong, Asmundur Oddsson, Gisli Masson, Olafur T. Magnusson, Tomas Gudbjartsson, Hreinn Stefansson, Patrick Sulem, Daniel Gudbjartsson, Unnur Thorsteinsdottir, Thorgeir E. Thorgeirsson and Kari Stefansson ()
Additional contact information
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
Elfar Ulfarsson: Landspitali University Hospital
Arnor Vikingsson: Landspitali, National University Hospital
Ragnheidur Hansdottir: University of Iceland
Karl O. Karlsson: University of Iceland
Thorunn Rafnar: deCODE Genetics/Amgen, Inc.
Ingileif Jonsdottir: deCODE Genetics/Amgen, Inc.
Michael L. Frigge: deCODE Genetics/Amgen, Inc.
Augustine Kong: deCODE Genetics/Amgen, Inc.
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
Hreinn Stefansson: deCODE Genetics/Amgen, Inc.
Patrick Sulem: deCODE Genetics/Amgen, Inc.
Daniel Gudbjartsson: deCODE Genetics/Amgen, Inc.
Unnur Thorsteinsdottir: deCODE Genetics/Amgen, Inc.
Thorgeir E. Thorgeirsson: deCODE Genetics/Amgen, Inc.
Kari Stefansson: deCODE Genetics/Amgen, Inc.

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14265

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