Neck and shoulder pain are prevalent musculoskeletal disorders that significantly impact the quality of life for a substantial portion of the global population. Studies have shown that women are more susceptible than men. This study aims to discover genetic variants associated with neck or shoulder pain through a genome-wide association study (GWAS), using data from 441,757 participants in the UK Biobank. The primary GWAS revealed five significant genetic loci (including two novel) associated with neck or shoulder pain, with the most significant single nucleotide polymorphism (SNP) being rs9889282 (p = 2.63 x 10-12) near CA10 on chromosome 17. Two novel significant associations were detected on chromosomes 18 and 14, with the top SNPs being rs4608411 (p = 8.20 x 10-9) near TCF4 and rs370565192 (p = 3.80 x 10-8) in DCAF5, respectively. The female-specific GWAS identified two significant loci including one near CA10 and one near LINC02770 on chromosome 1 with the top SNP being rs5779595 (p = 3.57 x 10-8). The male-specific GWAS identified one locus in SLC24A3 on chromosome 20 with the top SNP being rs16980973 (p = 6.52 x 10-9). The tissue expression analysis revealed a significant association between brain tissues and neck or shoulder pain. In summary, this study has identified novel genetic variants for neck or shoulder pain. Sex-stratified GWAS also suggested that gender played a role in the occurrence of the phenotype.

The authors have declared no competing interest.

This study was mainly funded by the Pioneer and Leading Goose R&D Program of Zhejiang Province 2023 with reference number 2023C04049 and Ningbo International Collaboration Program 2023 with reference number 2023H025. This work was also supported by the European Union's Horizon 2020 research and innovation programme under grant agreement No 633491 (DOLORisk).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The dataset we used was approved by the UK Biobank with a project number 89386. The ethics of this UK Biobank project was approved by the ethical committee of the University of Nottingham Ningbo China.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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This study adheres to all ethical guidelines and data protection protocols of the UK Biobank. The current study was conducted under approved UK Biobank data application number 89386. The summary statistics of the UK Biobank results on neck or shoulder pain can be accessed upon publication. Any other data relevant to the study that are not included in the article or its supplementary materials are available from the authors upon reasonable request.