SummaryIntroductionChronic pain is one of the most common and severe complications after surgery, affecting quality of life and overall wellbeing of patients. Several risk factors have been identified but the mechanisms of chronic postsurgical pain development remain unclear. This study aimed to identify single‐nucleotide polymorphisms associated with developing chronic postsurgical pain after abdominal surgery, one of the most common types of surgery.MethodsA genome‐wide association study was performed on 27,603 patients from the UK Biobank who underwent abdominal surgery. The robustness of identified loci was validated by split‐half validation analysis. Functionally related top loci were selected for expression validation in clinical samples of adhesions from patients with and without pain.ResultsOne locus (rs185545327) reached genome‐wide significance for association with chronic postsurgical pain development, and 10 loci surpassed the suggestively significant threshold (p < 1 × 10‐6). In the robustness analysis, eight loci had at least nominal significance. The loci passing the suggestively significant threshold were mapped to 15 genes, of which two loci contained pain‐related genes (SRPK2, PDE4D). Although marginally approaching statistical significance in the expression validation of clinical samples, the detection rate and expression level of PDE4D were modestly higher in patients with pain compared with those in the control group.DiscussionThis study provides preliminary evidence for genetic risk factors implicated in chronic postsurgical pain following abdominal surgery, particularly the PDE4D gene, which has been associated with pain in previous studies. The findings add to evidence suggesting potential for the future development of a clinically applicable tool for personalised risk prediction, aiding clinicians in stratifying patients and enhancing clinical decision‐making through individualised risk assessments.

中文翻译：

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英国生物样本库腹部手术后慢性术后疼痛的全基因组关联研究


摘要简介慢性疼痛是手术后最常见和最严重的并发症之一，影响患者的生活质量和整体健康状况。已经确定了几个风险因素，但慢性术后疼痛发展的机制仍不清楚。本研究旨在确定与腹部手术后发生慢性术后疼痛相关的单核苷酸多态性，腹部手术是最常见的手术类型之一。方法对来自英国生物样本库的 27,603 名接受腹部手术的患者进行了全基因组关联研究。通过分半验证分析验证了已鉴定基因座的稳健性。选择功能相关的顶部基因座，在有痛和无痛患者的粘连临床样本中进行表达验证。结果一个基因座 （rs185545327） 达到与慢性术后疼痛发展相关的全基因组显著性，10 个基因座超过了提示显著阈值 （p < 1 × 10-6）。在稳健性分析中，8 个基因座至少具有名义意义。通过提示显著阈值的基因座被定位到 15 个基因，其中两个基因座包含疼痛相关基因 （SRPK2 、 PDE4D）。尽管在临床样本的表达验证中略微接近统计学意义，但与对照组相比，疼痛患者 PDE4D 的检出率和表达水平略高。讨论本研究为与腹部手术后慢性术后疼痛有关的遗传风险因素提供了初步证据，特别是 PDE4D 基因，该基因在以前的研究中与疼痛有关。 这些发现增加了证据，表明未来有可能开发一种临床适用的个性化风险预测工具，帮助临床医生对患者进行分层，并通过个体化风险评估加强临床决策。