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

• Published in: Nature communications Vol. 8; no. 1; p. 14265
• Main Authors: Bjornsdottir, Gyda, Benonisdottir, Stefania, Sveinbjornsson, Gardar, Styrkarsdottir, Unnur, Thorleifsson, Gudmar, Walters, G. Bragi, Bjornsson, Aron, Olafsson, Ingvar H., Ulfarsson, Elfar, Vikingsson, Arnor, Hansdottir, Ragnheidur, Karlsson, Karl O., Rafnar, Thorunn, Jonsdottir, Ingileif, Frigge, Michael L., Kong, Augustine, Oddsson, Asmundur, Masson, Gisli, Magnusson, Olafur T., Gudbjartsson, Tomas, Stefansson, Hreinn, Sulem, Patrick, Gudbjartsson, Daniel, Thorsteinsdottir, Unnur, Thorgeirsson, Thorgeir E., Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.02.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/205/2138; 692/4023/1671; 692/499; Adult; Base Sequence; Body Height - genetics; Cancer; Chromosomes, Human, Pair 8 - genetics; Demography; Female; Genetic Loci; Genetic Predisposition to Disease; Genetic Variation; Genomes; Humanities and Social Sciences; Humans; Intervertebral Disc Degeneration - genetics; Intervertebral Disc Degeneration - surgery; Intervertebral Disc Displacement - genetics; Intervertebral Disc Displacement - surgery; Lumbar Vertebrae - pathology; Lumbar Vertebrae - surgery; Male; Middle Aged; multidisciplinary; Phenotype; Polymorphism, Single Nucleotide - genetics; Risk Factors; Sciatica - genetics; Science; Science (multidisciplinary); Iceland
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14265

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. Lumbar disc herniation (LDH) can cause persistent sciatica, and in some cases surgery is required to relieve symptoms. Here, the authors carry out a genome-wide association study using microdiscectomy as an indicator of severe LDH, and find a locus on chromosome 8 associated with this condition.