Medicine (Baltimore). 2025 May 2;104(18):e42331. doi: 10.1097/MD.0000000000042331.
ABSTRACT
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.
PMID:40324260 | DOI:10.1097/MD.0000000000042331
