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

Nat Commun. 2017 Feb 22;8:14265. doi: 10.1038/ncomms14265.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Body Height / genetics
  • Chromosomes, Human, Pair 8 / genetics*
  • Demography
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • 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
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Sciatica / genetics*

Supplementary concepts

  • Intervertebral disc disease