Background & Aims

Neck pain or shoulder pain are prevalent musculoskeletal disorders that significantly impact the quality of life for a substantial portion of the global population. In recent years, the age-standardized median prevalence of neck pain and shoulder pain was 27.0 and 37.8 per 1000 persons. Studies have shown that women are more susceptible to neck or shoulder pain than men. Despite the prevalence of neck or shoulder pain, the etiological factors, particularly the genetic underpinnings of these conditions, remain inadequately elucidated. The aim of this study is to discover genetic variants associated with neck or shoulder pain through a genome-wide association study (GWAS) using data from the UK Biobank.

Methods

In this study, data from 441,757 White British participants in the UK Biobank were used, of whom 101,305 participants we selected as the case group and all remaining samples were selected as the control group. The fastGWA function in GCTA was used for GWAS association analysis. In the primary GWAS analysis, the analysis was adjusted by age, gender, BMI and population principal components8. The sex-stratified separate GWASs were also performed. The GWAS results were annotated and visualized using the FUMA web application.

Results

The primary GWAS revealed five genetic loci associated with neck or shoulder pain at GWAS significant level. The most significant locus was near the CA10 gene on chromosome 17 with p=2.63E-12 for rs9889282. The second most significant locus was in the FOXP2 gene on chromosome 7 with p=1.69E-09 for rs34291892. The third locus was in the SLC39A8 gene on chromosome 4 with p=3.84E-09 for rs13135092. The fourth locus was next to the TCF4 gene on chromosome 18 with p=8.20E-09 for rs4608411. The fifth locus was in the DCAF5 gene on chromosome 14 with p=3.80E-08 for rs370565192. The forth and fifth loci are novel loci. The female-specific GWAS identified two significant loci including one near CA10 and one near the LINC02770 gene on chromosome 1 with p=3.57E-08 for rs1651359966. The male-specific GWAS found a single locus in the SLC24A3 gene on chromosome 20 with p=6.52E-09 for rs16980973. Tissue expression analysis revealed a significant association between brain and neck or shoulder pain.

Conclusions

We have identified five genetic loci including two novel ones associated with neck or shoulder pain in the primary GWAS and one novel locus for both male-specific and female-specific GWAS, respectively. These findings hold promise for personalized medicine approaches and the development of targeted interventions for individuals predisposed to or experiencing neck and shoulder pain.

References

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2.Forrest, M. et al. Functional analysis of TCF4 missense mutations that cause Pitt–Hopkins syndrome. Human Mutation 33, 1676–1686 (2012).

3.GCTA: a tool for genome-wide complex trait analysis – PubMed. https://pubmed.ncbi.nlm.nih.gov/21167468/.

4.Hanvold, T. N. et al. A longitudinal study on risk factors for neck and shoulder pain among young adults in the transition from technical school to working life. Scandinavian Journal of Work, Environment & Health 40, 597–609 (2014).

5.Kazeminasab, S. et al. (2022) ‘Neck pain: global epidemiology, trends and risk factors’, BMC Musculoskeletal Disorders, 23(1), p. 26. Available at: https://doi.org/10.1186/s12891-021-04957-4.
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7.Liégeois, F. et al. Language fMRI abnormalities associated with FOXP2 gene mutation. Nat Neurosci 6, 1230–1237 (2003).

8.Lucas, J. et al. (2022) ‘A systematic review of the global prevalence and incidence of shoulder pain’, BMC musculoskeletal disorders, 23(1), p. 1073. Available at: https://doi.org/10.1186/s12891-022-05973-8.
9.Meng, W. et al. (2020) ‘A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank’, Human Molecular Genetics, 29(8), pp. 1396–1404. Available at: https://doi.org/10.1093/hmg/ddaa058.

10.Nebert, D. W. & Liu, Z. SLC39A8 gene encoding a metal ion transporter: discovery and bench to bedside. Human Genomics 13, 51 (2019).

11.Shariat, A. et al. Prevalence rate of neck, shoulder and lower back pain in association with age, body mass index and gender among Malaysian office workers. Work 60, 191–199 (2018).

12.Sterky, F. H. et al. Carbonic anhydrase-related protein CA10 is an evolutionarily conserved pan-neurexin ligand. Proceedings of the National Academy of Sciences 114, E1253–E1262 (2017).

Presenting Author

Yiwen Tao

Poster Authors

Yiwen Tao

BSc(Hons)

University of Nottingham Ningbo

Lead Author

E-mail

Qi Pan

University of Nottingham Ningbo China

Lead Author

E-mail

Tengda Cai

Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute

Lead Author

E-mail

Weihua Meng

Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute

Lead Author

E-mail

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Neck Pain