Department of Human Genetics, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Pharmacogenomics J. 2023 Nov;23(6):161-168. doi: 10.1038/s41397-023-00314-x. Epub 2023 Aug 16.
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). Suggestive significant (P < 1 × 10) 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.
肌肉骨骼疼痛的药物治疗始于 NSAIDs，然后是弱阿片类或强阿片类药物，直到疼痛得到控制。然而，由于个体间的差异，治疗效果通常并不令人满意。为了研究治疗效果差异的遗传成分，我们在英国生物库中对约 23000 名患有肌肉骨骼疼痛的参与者进行了全基因组关联研究（GWAS）。将 NSAID 与阿片类药物使用者进行比较，以反映 NSAIDs 的治疗效果。我们在 4 号染色体上发现了一个全基因组显著关联（rs549224715，P=3.88×10）。提示显著（P<1×10）的基因座被功能注释到 18 个靶基因，包括与神经病理性疼痛过程或肌肉骨骼发育相关的四个基因。通路和网络分析确定了与免疫相关的过程和 EGFR 的（假定）中枢作用。然而，这项研究应该被视为阐明肌肉骨骼疼痛治疗遗传背景的第一步。
