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.

肌肉骨骼疼痛的药物治疗首先使用非甾体抗炎药，然后使用弱或强的阿片类药物，直到疼痛得到控制。然而，由于个体差异，治疗效果往往不尽如人意。为了调查治疗结果差异的遗传因素，我们对来自英国生物银行的约 23,000 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)。将非甾体抗炎药与阿片类药物使用者进行比较，以反映非甾体抗炎药的治疗结果。我们在 4 号染色体上发现了一个全基因组显着命中（rs549224715，P  = 3.88 × 10 ^-8）。提示性显着（P  < 1 × 10 ^-6）位点被功能注释到 18 个目标基因，其中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免疫相关过程和EGFR的（假定的）核心作用。然而，这项研究应被视为阐明肌肉骨骼疼痛治疗遗传背景的第一步。