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

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

Title: Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation
Author: Bjornsdottir, Gyda   orcid.org/0000-0002-8100-0306
Benonisdottir, Stefania   orcid.org/0000-0001-5019-514X
Sveinbjornsson, Gardar   orcid.org/0000-0003-2429-9468
Styrkarsdottir, Unnur   orcid.org/0000-0001-8146-8278
Þorleifsson, Guðmar
Walters, G. Bragi   orcid.org/0000-0002-5415-6487
Björnsson, Aron
Ólafsson, Ingvar Hákon
Úlfarsson, Elfar
Víkingsson, Arnór
... 16 more authors Show all authors
Date: 2017-02-22
Language: English
Scope: 14265
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Verkfræði- og náttúruvísindasvið (HÍ)
School of Engineering and Natural Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Tannlæknadeild (HÍ)
Faculty of Odontology (UI)
Raunvísindastofnun (HÍ)
Science Institute (UI)
Series: Nature Communications;8
ISSN: 2041-1723
DOI: 10.1038/ncomms14265
Subject: Genome-wide association studies; Musculoskeletal system; Risk factors; Erfðafræði; Rannsóknir; Stoðkerfi (líffærafræði); Áhættuþættir
URI: https://hdl.handle.net/20.500.11815/294

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Bjornsdottir, G. et al. Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation. Nat. Commun. 8, 14265 doi: 10.1038/ncomms14265 (2017).


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.


Data supporting the findings of this study are available within the article and its Supplementary Information files. Summary level data of markers tested for association is described in Scientific data as of 2015 with the identifier http://dx.doi.org/10.1038/sdata.2015.11 (ref. 64). Whole-genome sequencing summary data are available at the European Variant Archive (EVA, https://www.ebi.ac.uk/eva/) under the accession code PRJEB8636. GTEx data (http://www.gtexportal.org) accessed 8 August 2016; LD Score Database (ftp://atguftp.mgh.harvard.edu/brendan/1k_eur_r2_hm3snps_se_weights.RDS) accessed 23 June 2015; GWAS catalogue (https://www.ebi.ac.u/gwas/home) accessed 8 September 2016.


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