#0773

Causal Association Between Body Mass Index and Kidney Stone Disease in Taiwanese: A Mendelian Randomization Study

P. Hsu¹, M. Lee², J. Geng²

¹Kaohsiung Medical University Chung-Ho Memorial Hospital, Department of General Medicine, Kaohsiung City, Taiwan
²Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital, Department of Urology, Kaohsiung City, Taiwan

Introduction:

Kidney stone disease (KSD) is a common urological disorder with increasing incidence worldwide. Previous observational studies have reported an association between body mass index (BMI) and KSD, yet the causal relationship remains uncertain, especially in Asian populations. Thus, this study aims to investigate the causal effect of BMI on KSD risk in Taiwanese individuals using a two-sample Mendelian Randomization (MR) approach.

Material and methods:

We conducted genome-wide association studies (GWAS) for BMI and KSD using data from Taiwanese cohorts. Significant SNPs associated with BMI were selected as instrumental variables after validation in our population. Several MR methods, including inverse variance weighted (IVW), weighted median, penalized MR, and MR-Egger regression, were applied to estimate the causal effect. Robustness and pleiotropy were assessed to ensure the reliability of findings.

Results:

A total of 16 BMI-associated SNPs validated in our Taiwanese cohort were used as instrumental variables for Mendelian Randomization (MR) analysis. The penalized robust IVW method demonstrated a significant positive causal effect of BMI on KSD risk (β = 0.77, 95% CI: 0.20–1.33, P = 0.008), suggesting that higher genetically predicted BMI increases the risk of KSD. Similar trends were observed across other MR methods, including the weighted median (β = 0.78, P = 0.050), penalized weighted median (β = 0.80, P = 0.042), and robust IVW (β = 0.76, P = 0.008). In contrast, the MR-Egger regression did not show a significant association (β = 0.21, P = 0.84) but indicated no evidence of directional pleiotropy (intercept P = 0.61). Sensitivity analyses supported the robustness and consistency of the findings, suggesting that elevated BMI is causally associated with an increased risk of KSD in Taiwanese individuals.