title: Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation.
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.
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Gyda
authors.initials: G
authors.lastname: Bjornsdottir
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Benonisdottir
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Gardar
authors.initials: G
authors.lastname: Sveinbjornsson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Unnur
authors.identifier: 0000-0001-8146-8278
authors.initials: U
authors.lastname: Styrkarsdottir
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: G Bragi
authors.identifier: 0000-0002-5415-6487
authors.initials: GB
authors.lastname: Walters
authors.affiliation: Department of Neurosurgery, Landspitali University Hospital, Reykjavik IS-101, Iceland.
authors.forename: Aron
authors.initials: A
authors.lastname: Bjornsson
authors.affiliation: Department of Neurosurgery, Landspitali University Hospital, Reykjavik IS-101, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik IS-101, Iceland.
authors.forename: Ingvar H
authors.initials: IH
authors.lastname: Olafsson
authors.affiliation: Department of Neurosurgery, Landspitali University Hospital, Reykjavik IS-101, Iceland.
authors.forename: Elfar
authors.initials: E
authors.lastname: Ulfarsson
authors.affiliation: Department of Medicine, Landspitali, National University Hospital, Reykjavik IS-101, Iceland.|Thraut Fibromyalgia Clinic, Reykjavik IS-101, Iceland.
authors.forename: Arnor
authors.initials: A
authors.lastname: Vikingsson
authors.affiliation: Department of Dentistry, University of Iceland, Reykjavik IS-101, Iceland.
authors.forename: Ragnheidur
authors.initials: R
authors.lastname: Hansdottir
authors.affiliation: Department of Dentistry, University of Iceland, Reykjavik IS-101, Iceland.
authors.forename: Karl O
authors.initials: KO
authors.lastname: Karlsson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik IS-101, Iceland.
authors.forename: Ingileif
authors.initials: I
authors.lastname: Jonsdottir
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Frigge
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.|School of Engineering and Natural Sciences, Science Institute, University of Iceland, Reykjavik IS-101, Iceland.
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Asmundur
authors.identifier: 0000-0002-4606-5163
authors.initials: A
authors.lastname: Oddsson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Gisli
authors.initials: G
authors.lastname: Masson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Olafur T
authors.initials: OT
authors.lastname: Magnusson
authors.affiliation: Faculty of Medicine, University of Iceland, Reykjavik IS-101, Iceland.|Department of Surgery, Landspitali University Hospital, Reykjavik IS-101, Iceland.
authors.forename: Tomas
authors.initials: T
authors.lastname: Gudbjartsson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Patrick
authors.identifier: 0000-0001-7123-6123
authors.initials: P
authors.lastname: Sulem
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.|School of Engineering and Natural Sciences, Science Institute, University of Iceland, Reykjavik IS-101, Iceland.
authors.forename: Daniel
authors.identifier: 0000-0002-5222-9857
authors.initials: D
authors.lastname: Gudbjartsson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik IS-101, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.
authors.forename: Thorgeir E
authors.initials: TE
authors.lastname: Thorgeirsson
authors.affiliation: deCODE Genetics/Amgen, Inc., Reykjavik IS-101, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik IS-101, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000328:Adult; D001483:Base Sequence; D001827:Body Height / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003710:Demography; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000601:surgery; D007405:Intervertebral Disc Displacement / Q000235:genetics* / Q000601:surgery; D008159:Lumbar Vertebrae / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012585:Sciatica / Q000235:genetics*