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Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes
  1. Maxim Freidin1,
  2. Minna Kraatari2,3,4,
  3. Sini Skarp2,3,
  4. Juhani Määttä1,4,
  5. Johannes Kettunen2,5,6,
  6. Jaakko Niinimäki4,7,
  7. Jaro Karppinen2,4,8,
  8. Frances Williams1,
  9. Minna Männikkö9
  1. 1 Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College London, London, UK
  2. 2 Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
  3. 3 Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
  4. 4 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
  5. 5 Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
  6. 6 National Institute for Health and Welfare, Helsinki, Finland
  7. 7 Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
  8. 8 Finnish Institute of Occupational Health, Oulu, Finland
  9. 9 Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland
  1. Correspondence to Dr Minna Männikkö, Northern Finland Birth Cohort Studies, Faculty of Medicine, Aapistie 5 / P.O. Box 5000, 90014 University of Oulu, Finland; minna.ruddock{at}


Background Low back pain (LBP) is a common disabling condition. Lumbar disc degeneration (LDD) may be a contributing factor for LBP. Modic change (MC), a distinct phenotype of LDD, is presented as a pathological bone marrow signal change adjacent to vertebral endplate on MRI. It is strongly associated with LBP and has heritability around 30%. Our objective was to identify genetic loci associated with MC using a genome-wide meta-analysis.

Methods Presence of MC was evaluated in lumbar MRI in the Northern Finland Birth Cohort 1966 (n=1182) and TwinsUK (n=647). Genome-wide association analyses were carried out using linear regression model. Inverse-variance weighting approach was used in the meta-analysis.

Results A locus associated with MC (p<5e-8) was found on chromosome 9 with the lead SNP rs1934268 in an intron of the PTPRD gene. It is located in the binding region of BCL11A, SPI1 and PBX3 transcription factors. The SNP was nominally associated with LBP in TwinsUK (p=0.001) but not associated in the UK Biobank (p=0.914). Suggestive signals (p<1e-5) were identified near XKR4, SCIN, MGMT, DLG2, ZNF184 and OPRK1.

Conclusion PTPRD is a novel candidate gene for MC that may act via the development of cartilage or nervous system; further work is needed to define the mechanisms underlying the pathways leading to development of MC. This is the first genome-wide meta-analysis of MC, and the results pave the way for further studies on the genetic factors underlying the various features of spine degeneration and LBP.

  • disc degeneration
  • GWAS
  • meta-analysis
  • Modic change
  • genetics

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  • MF, MK and SS contributed equally.

  • FW and MM contributed equally.

  • Contributors MK, MF, SS, JKe, JKa, MM and FW designed the study. MK, JM, JN and JKa collected the data. MK, MF and SS performed the data analysis and drafted the manuscript. MM and FW coordinated the study. All authors commented on the manuscript and agreed on the final version to be published.

  • Funding This study was supported by EU FP7 project Pain_OMICS (grant agreement #602736). TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, the National Institute for Health Research-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. NFBC1966 data collection at 46y received financial support from the University of Oulu (Grant no. 24000692), Oulu University Hospital (Grant no. 24301140) and the European Regional Development Fund (Grant no. 539/2010 A31592). The UK Biobank Resource data were used under the project ’Genetic and epidemiological analyses of low back pain' (#18219).

  • Competing interests None declared.

  • Ethics approval St Thomas’ Hospital Research Ethics Committee and The Ethical Committee of the Northern Ostrobothnia Hospital District have approved the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Obtained.