Kidney stone disease (KSD) is a common urological disorder with an increasing incidence worldwide. Previous observational studies have reported an association between body mass index (BMI) and KSD; however, the causal relationship remains uncertain, particularly in Asian populations. This study aimed to investigate the causal effect of BMI on KSD risk in Taiwanese individuals using a Mendelian randomization (MR) approach.
BMI-associated single nucleotide polymorphisms (SNPs) were identified through a literature review and validated in Taiwanese cohorts (n = 107,191). Significant SNPs (P-value < 0.05) were selected as instrumental variables for MR analysis, with KSD as the outcome. Several MR methods, including inverse variance weighted (IVW), median-based, robust, and MR-Egger approaches, were applied to estimate the causal effect.
A total of 17 BMI-associated SNPs validated in the Taiwanese cohort were used as instrumental variables in the MR analysis. The penalized IVW model demonstrated a significant positive association between genetically predicted BMI and KSD risk (OR = 2.16, 95% CI: 1.22-3.81, P-value = 0.008). Similar results were observed using robust IVW (OR = 2.13, 95% CI: 1.25-3.62, P-value = 0.005) and weighted median approaches (P-value = 0.050 and 0.042). No evidence of directional pleiotropy was detected.
Our findings provide genetic evidence supporting a causal association between higher BMI and increased KSD risk in Taiwanese individuals, suggesting that weight management may play an important role in KSD prevention. Further studies are needed to investigate the underlying biological mechanisms, population-specific genetic susceptibilities, and effective preventive strategies for obesity-related KSD.
International journal of medical sciences. 2026 Mar 17*** epublish ***
Ming-Ru Lee, Po-Yu Hsu, Szu-Chia Chen, Shu-Pin Huang, Jiun-Hung Geng
Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 812015, Taiwan., Department of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan., Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812015, Taiwan., Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.