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

Song Li; Geert Poelmans; Regina L.M. van Boekel; Marieke J.H. Coenen

doi:10.1038/s41397-023-00314-x

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

Song Li, Geert Poelmans, Regina L.M. van Boekel, Marieke J.H. Coenen^*

^*Corresponding author for this work

Clinical Chemistry

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

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.

Original language	English
Pages (from-to)	161-168
Number of pages	8
Journal	Pharmacogenomics Journal
Volume	23
Issue number	6
DOIs	https://doi.org/10.1038/s41397-023-00314-x
Publication status	Published - Nov 2023

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.

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

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