Causal effects of obesity on urolithiasis and the mediating role of inflammatory factors: A two-sample Mendelian randomization study.

This study aimed to investigate the genetic causal relationship between obesity and urolithiasis using a two-sample Mendelian randomization (MR) approach. It further explored the potential mediating role of inflammatory factors in this causal pathway. Single nucleotide polymorphisms (SNPs) associated with body mass index, waist-to-hip ratio, and urolithiasis were obtained from publicly available genome-wide association study datasets and employed as instrumental variables. A bidirectional two-sample MR analysis was performed to assess the causal effect of obesity on the risk of urolithiasis. The inverse variance weighted method served as the primary analytical strategy, supplemented by sensitivity analyses using the simple mode, weighted median, weighted mode, and MR-Egger regression methods. To explore potential mediation, mediation MR and multivariable MR analyses were conducted. Additional sensitivity analyses were carried out to evaluate the robustness of the findings. MR analysis revealed a significant positive causal associations of both body mass index (odds ratio = 1.190, 95% confidence interval: 1.082-1.308, P = 3.27 × 10-4) and waist-to-hip ratio (odds ratio = 1.245, 95% confidence interval: 1.107-1.401, P = 2.63 × 10-4) with urolithiasis. Mediation analysis identified fibroblast growth factor 21 as a significant mediator in the pathway linking obesity to urolithiasis. This study provides genetic evidence supporting a causal association between obesity and an increased risk of urolithiasis. The inflammatory marker fibroblast growth factor 21 may partially mediate this relationship.