The causal impact of smoking behavior on osteoarthritis: a Mendelian randomization analysis

Although smoking and osteoarthritis (OA) have been linked in a number of studies, the exact cause of the association is still unknown and the conclusion is controversial. The purpose of this study was to use Mendelian randomization (MR) analysis to investigate the causal relationship between smoking phenotypes and OA risk from a genetically informed standpoint.

As instrumental variables (IVs) based on single nucleotide polymorphisms (SNPs), this study used the summary-level data of corresponding genome-wide association study (GWAS) for five smoking phenotypes involving 1,694,781 samples. The outcomes comprised both a discovery and a replication cohort. The discovery MR analysis involved 12 OA traits (177,517 cases and 649,173 controls) while the replication MR analysis incorporated an additional OA GWAS dataset consisting of 36,185 cases and 135,185 controls. The main analytic approach we used was the inverse variance weighted (IVW) method. MR Egger, Weighted median, Weighted mode, and Simple mode were among the other methods that were tested. We conducted meta-analysis to combine the MR results. To confirm the robustness of the results, sensitivity analysis using Leave-One-Out (LOO), level pleiotropy testing (MR Egger intercept test and MR-PRESSO), and heterogeneity testing were performed.

Summary-level MR analysis revealed a positive correlation between genetic predisposition for smoking and the likelihood of developing OA. The meta-analysis merge showed that smoking initiation increased the risk of knee OA by 20%, hip OA by 16%, and knee/hip OA by 19% (all p < 0.001). Similarly, lifetime smoking elevated the risk of knee OA by 101%, hip OA by 55%, and knee/hip OA by 84% (all p < 0.001). The sensitivity analysis's findings reinforced the reliability of these findings.

According to our research, smoking increases the likelihood of developing OA from a genetic standpoint. Reducing tobacco use could, therefore, be beneficial in lowering the incidence of OA.