Association of DNA methylation and musculoskeletal spinal pain at four timepoints during adolescence and early adulthood

Abstract

Background: This study examined the association between epigenetic genome-wide DNA methylation with mechanism-based phenotypes of spinal pain from adolescence through early adulthood, accounting for confounders. Research design and methods: We investigated the relationship between the timing of spinal pain at 14, 17, 22, and 27 years and blood DNA methylation at 17 years in the Raine Study Gen2 cohort. We analyzed three phenotypes of spinal pain (neck pain only, low back pain only, neck and low back pain) compared to participants with no spinal pain using linear mixed effects models. Results: We identified four genome-wide significant loci (3 neck, 1 back), all at age 22, and none from the other time points or with the combined neck and low back pain. The top locus for neck pain age 22 was cg06573902 (β = 0.0058, p-value 1.34E−8) in the gene TOP1 (DNA Topoisomerase I). The top locus for low back pain at age 22, was cg14080518 (β = 0.0072, p-value = 5.36E−8), located in the gene SMURF1 (SMAD Specific E3 Ubiquitin Protein Ligase 1). Conclusion: While more basic research is required, the existence of mechanistic links could facilitate better screening and novel management strategies for those with spinal pain.

Document Type

Journal Article

Date of Publication

1-1-2025

PubMed ID

41362942

Publication Title

Epigenomics

Publisher

Taylor & Francis

School

Nutrition and Health Innovation Research Institute

Comments

Beales, D., Waller, R., Chia, J. Y. N., Lim, L. M., Tan, H. Y., Tan, J. L., Huang, R., Straker, L., & Melton, P. E. (2025). Association of DNA methylation and musculoskeletal spinal pain at four timepoints during adolescence and early adulthood. Epigenomics, 17(18), 1411–1422. https://doi.org/10.1080/17501911.2025.2596575

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Link to publisher version (DOI)

10.1080/17501911.2025.2596575