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

Author Identifier (ORCID)

Rae Chi Huang's ORCID record ORCID Logo

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.

Keywords

Biopsychosocial, DNA methylation, epigenetic epidemiology, epigenetics and disease, low back pain, neck 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

Funding Information

The core management of the Raine Study is funded by The University of Western Australia, Curtin University, Telethon Kids Institute, Women and Infants Research Foundation, Edith Cowan University, Murdoch University and The University of Notre Dame Australia. The Pawsey Supercomputing Centre provided computation resources to carry out analyses required with funding from the Australian Government and the Government of Western Australia. The Gen2-14 year follow-up data utilized for this project was supported by a NHMRC [Sly et al., ID 211912], NHMRC Program Grant [Stanley et al., ID 003209], The Raine Medical Research Foundation and NHMRC [Straker et al., ID 323200]. The Gen2-17 year follow-up data utilized for this project was supported by a NHMRC Program Grant [Stanley et al., ID 353514], NHMRC [Beilin et al., ID 403981], NHMRC [Straker et al., ID 323200], NHMRC [Palmer et al., ID 572613], NHMRC [Huang et al., ID 1059711] and Canadian Institutes of Health Research - CIHR [Lye et al., MOP-82893]. The Gen2-22 year follow-up data utilized for this project was supported by The Centre for Sleep Science, School of Anatomy, Physiology & Human Biology, The University of Western Australia, NHMRC [Eastwood et al., ID 1027449] and NHMRC [Straker et al., ID 1044840]. The Gen2-22 year follow-up data utilized for this project was supported by the NHMRC [Mori et al., ID 1102106], NHMRC [Eastwood et al., ID 1109057], National Heart Foundation (Mori et al., ID 102301), Cancer Australia [Stone et al., ID 1147677], Royal Perth Hospital Medical Research Foundation, The Heart Foundation, WA Branch, Lions Eye Institute, Curtin University, School of Population and Global Health, The University of Western Australia, Division of Obstetrics and Gynaecology, The University of Western Australia and John Olynyk. Rae-Chi Huang is supported by NHMRC fellowship [Grant Number 1053384] NHMRC EU [Grant Number 114285]. Phillip E. Melton is supported by NHMRC grant [Grant number 2001203].

Funding received from the National Health and Medical Research Council (NHMRC)

211912, 3209, 323200, 353514, 403981, 572613, 1059711, 1027449, 1044840, 1102106, 1109057, 1053384, 114285, 2001203

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subscription content

Content Type

Metadata only

Recommended Citation

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