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

2017; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/ncomms14265

2041-1723

Gyða Björnsdóttir, Stefania Benónísdóttir, Garðar Sveinbjörnsson, Unnur Styrkársdóttir, Guðmar Þorleifsson, G. Bragi Walters, Aron Hjalti Björnsson, Ingvar Hákon Ólafsson, Elfar Úlfarsson, Arnór Víkingsson, Ragnheiður Hansdottir, Karl Orn Karlsson, Þórunn Rafnar, Ingileif Jónsdóttir, Michael L. Frigge, Augustine Kong, Ásmundur Oddsson, Gísli Másson, Ólafur Þ. Magnússon, Tómas Guðbjartsson, Hreinn Stefánsson, Patrick Sulem, Daníel F. Guðbjartsson, Unnur Þorsteinsdóttir, Thorgeir E. Thorgeirsson, Kāri Stefánsson,

Spine and Intervertebral Disc Pathology

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.