University of Oulu

Freidin M, Kraatari M, Skarp S, et al., Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes, Journal of Medical Genetics 2019;56:420-426

Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes

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Author: Freidin, Maxim1; Kraatari, Minna2,3,4; Skarp, Sini2,3;
Organizations: 1Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King’s College London, London, UK
2Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
3Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
4Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
5Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
6National Institute for Health and Welfare, Helsinki, Finland
7Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
8Finnish Institute of Occupational Health, Oulu, Finland
9Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: BMJ, 2019
Publish Date: 2019-11-22


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.

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Series: Journal of medical genetics
ISSN: 0022-2593
ISSN-E: 1468-6244
ISSN-L: 0022-2593
Volume: 56
Issue: 7
Pages: 420 - 426
DOI: 10.1136/jmedgenet-2018-105726
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
3126 Surgery, anesthesiology, intensive care, radiology
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).
Copyright information: © author(s) (or their employer(s)) 2019. no commercial re-use. See rights and permissions. Published by BMJ.