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Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects
  1. Frances M K Williams1,
  2. Aruna T Bansal2,
  3. Joyce B van Meurs3,4,
  4. Jordana T Bell1,
  5. Ingrid Meulenbelt4,5,
  6. Pradeep Suri6,
  7. Fernando Rivadeneira3,4,
  8. Philip N Sambrook7,
  9. Albert Hofman8,
  10. Sita Bierma-Zeinstra9,
  11. Cristina Menni1,
  12. Margreet Kloppenburg10,
  13. P Eline Slagboom4,5,
  14. David J Hunter7,
  15. Alex J MacGregor1,
  16. Andre G Uitterlinden3,
  17. Tim D Spector1
  1. 1Department Twin Research and Genetic Epidemiology, King's College London, London, UK
  2. 2Acclarogen Ltd, St John's Innovation Centre, Cambridge, UK
  3. 3Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
  4. 4The Netherlands Genomics Initiative sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/Rotterdam, The Netherlands
  5. 5Department of Molecular Epidemiology, Leiden University Medical Center, Leiden/Rotterdam, The Netherlands
  6. 6VA Boston Healthcare System, Harvard Medical School, Spaulding Rehabilitation Hospital, New England Baptist Hospital, Boston, USA
  7. 7Department of Rheumatology, University of Sydney and Royal North Shore Hospital, Sydney, Australia
  8. 8Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
  9. 9Department of General Practice, Erasmus MC, Rotterdam, The Netherlands
  10. 10Department of Rheumatology and Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Frances M K Williams, Department Twin Research and Genetic Epidemiology, King's College London, St Thomas Hospital, Westminster Bridge Road, London SE1 7EH, UK; frances.williams{at}


Objective Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem. LDD is characterised by disc space narrowing and osteophyte growth at the circumference of the disc. To date, the agnostic search of the genome by genome-wide association (GWA) to identify common variants associated with LDD has not been fruitful. This study is the first GWA meta-analysis of LDD.

Methods We have developed a continuous trait based on disc space narrowing and osteophytes growth which is measurable on all forms of imaging (plain radiograph, CT scan and MRI) and performed a meta-analysis of five cohorts of Northern European extraction each having GWA data imputed to HapMap V.2.

Results This study of 4600 individuals identified four single nucleotide polymorphisms with p<5×10−8, the threshold set for genome-wide significance. We identified a variant in the PARK2 gene (p=2.8×10−8) associated with LDD. Differential methylation at one CpG island of the PARK2 promoter was observed in a small subset of subjects (β=8.74×10−4, p=0.006).

Conclusions LDD accounts for a considerable proportion of low back pain and the pathogenesis of LDD is poorly understood. This work provides evidence of association of the PARK2 gene and suggests that methylation of the PARK2 promoter may influence degeneration of the intervertebral disc. This gene has not previously been considered a candidate in LDD and further functional work is needed on this hitherto unsuspected pathway.

  • Gene Polymorphism
  • Low Back Pain
  • Magnetic Resonance Imaging

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: and

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