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Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank

The Pharmacogenomics Journal volume 23, pages 161–168 (2023)Cite this article

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Abstract

The pharmacological management of musculoskeletal pain starts with NSAIDs, followed by weak or strong opioids until the pain is under control. However, the treatment outcome is usually unsatisfying due to inter-individual differences. To investigate the genetic component of treatment outcome differences, we performed a genome-wide association study (GWAS) in ~23,000 participants with musculoskeletal pain from the UK Biobank. NSAID vs. opioid users were compared as a reflection of the treatment outcome of NSAIDs. We identified one genome-wide significant hit in chromosome 4 (rs549224715, P = 3.88 × 10−8). Suggestive significant (P < 1 × 10−6) loci were functionally annotated to 18 target genes, including four genes linked to neuropathic pain processes or musculoskeletal development. Pathway and network analyses identified immunity-related processes and a (putative) central role of EGFR. However, this study should be viewed as a first step to elucidate the genetic background of musculoskeletal pain treatment.

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Fig. 1: Flowchart of the phenotype definition.
Fig. 2: Q-Q plot and Manhattan plot of primary analysis for compating NSAID versus opioid users.

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Data availability

Summary statistics of the primary analysis are available at DANS archive (https://doi.org/10.17026/dans-xns-un6c). Gene mapping results are available at FUMA (https://fuma.ctglab.nl/browse/378).

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Acknowledgements

The authors thank Ward De Witte for assistance with data analysis. This research has been conducted using the UK Biobank Resource under Application Number 52524. The authors are grateful to the UK Biobank participants for making such research possible.

Funding

SL was supported by China Scholarship Council (CSC) Grant number 201908130179. This work was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative. This work is part of the research program Computing Time National Computing Facilities Processing Round pilots 2018 with project number 17666, which is (partly) financed by the Dutch Research Council (NWO).

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Author notes

  1. Marieke J. H. Coenen

    Present address: Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands

Authors and Affiliations

  1. Department of Human Genetics, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands

    Song Li & Marieke J. H. Coenen

  2. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands

    Geert Poelmans

  3. Department of Anesthesiology, Pain and Palliative Medicine, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands

    Regina L. M. van Boekel

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Contributions

SL analyzed the data and prepared the manuscript. GP contributed to the pathway and network analysis and revised the manuscript. RLMvB contributed to the phenotype definition and revised the manuscript. MJHC conceptualized the study, supervised the overall project, and revised the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Marieke J. H. Coenen.

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Li, S., Poelmans, G., van Boekel, R.L.M. et al. Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank. Pharmacogenomics J 23, 161–168 (2023). https://doi.org/10.1038/s41397-023-00314-x

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