Xu Zhouliang, Chen Ganlu, Xie Daofen, Yan Xiaoyan, Li Shuangyue
Department of Pain Management, Lihuili Hospital of Ningbo Medical Centre, Ningbo, China.
Department of Pain Management, Jiangwan Hospital of Hongkou District, Shanghai, China.
Medicine (Baltimore). 2025 May 2;104(18):e42331. doi: 10.1097/MD.0000000000042331.
A plethora of research has identified a comorbid association between smoke and an elevated risk of knee pain. Despite these findings, the causal link between genetically influenced smoke and the risk of knee pain remains to be elucidated. Considering this knowledge gap, we undertook a Mendelian randomization (MR) study to delineate the potential causal relationship. The instrumental variables were derived from genome-wide association studies (GWAS). We procured summary statistics for ever smoked from a GWAS dataset (280,508 cases and 180,558 controls, dataset: ukb-b-20261) to represent the exposure. The outcome was determined by GWAS data for knee pain for 3+ months, encompassing 76,910 cases and 20,979 controls (dataset: ukb-b-8906). The primary MR method employed was the inverse-variance weighted approach. Assessments for pleiotropy and heterogeneity were conducted utilizing the MR pleiotropy residual sum and outlier test, the MR-Egger intercept test, the leave-one-out analysis, and the Cochran Q test. There was a statistically significant genetic causal effect of smoke on the increased risk of knee pain (odds ratio = 1.08, 95% confidence interval = 1.01-1.16, P = .014]. Cochran Q statistic showed no heterogeneity (Q P = .66). The leave-one-out analysis chart, the global test P value in MR-pleiotropy residual sum, and outlier revealed no significant pleiotropy (global test P = 0.53). The intercept P value in MR-Egger revealed no significant pleiotropy (intercept P = 0.66). Our MR study showed no pleiotropy or heterogeneity. The findings from our study point toward an association between genetic predisposition to smoke and the incidence of knee pain. This genetic association underscores the clinical relevance of our findings, indicating that interventions aimed at smoking cessation could be particularly beneficial for those individuals who are predisposed to smoking or are at risk of developing knee pain.
大量研究已证实吸烟与膝关节疼痛风险升高之间存在共病关联。尽管有这些发现，但基因影响的吸烟与膝关节疼痛风险之间的因果关系仍有待阐明。考虑到这一知识空白，我们进行了一项孟德尔随机化（MR）研究，以确定潜在的因果关系。工具变量来自全基因组关联研究（GWAS）。我们从一个GWAS数据集（280,508例病例和180,558例对照，数据集：ukb-b-20261）中获取曾经吸烟的汇总统计数据，以代表暴露情况。结局由3个月以上膝关节疼痛的GWAS数据确定，包括76,910例病例和20,979例对照（数据集：ukb-b-8906）。采用的主要MR方法是逆方差加权法。利用MR多效性残差和离群值检验、MR-Egger截距检验、留一法分析和Cochran Q检验对多效性和异质性进行评估。吸烟对膝关节疼痛风险增加存在统计学显著的遗传因果效应（优势比=1.08，95%置信区间=1.01-1.16，P=0.014）。Cochran Q统计量显示无异质性（Q P=0.66）。留一法分析图、MR多效性残差和离群值中的全局检验P值均未显示显著的多效性（全局检验P=0.53）。MR-Egger中的截距P值未显示显著的多效性（截距P=0.66）。我们的MR研究未显示多效性或异质性。我们的研究结果表明，吸烟的遗传易感性与膝关节疼痛的发生率之间存在关联。这种遗传关联强调了我们研究结果的临床相关性，表明针对戒烟的干预措施可能对那些有吸烟倾向或有患膝关节疼痛风险的个体特别有益。
