The potential causal relationship between BMI, T1D, urolithiasis, and hydronephrosis in European ancestry: A Mendelian randomization analysis

Abstract

Body mass index (BMI), type 1 diabetes (T1D), urolithiasis, and hydronephrosis are interrelated. Our aim was to analyze their causal relationships at the genetic level. Mendelian randomization is an instrumental variable analysis method that follows Mendel genetic law of random allocation of parental alleles to offspring. In observational studies, genetic variants are used as instrumental variables to infer causal relationships between exposure factors and study outcomes. All the genome-wide association study data in our study were publicly available and from published genome-wide association studies, UK Biobank, and FinnGen. Random-effects inverse variance weighted was the primary analysis method, with R Egger, weighted median, and weighted mode as supplementary methods. We examined heterogeneity, horizontal pleiotropy, and the influence of individual single nucleotide polymorphisms on the analysis. We further explored the causal relationships between BMI, T1D, urolithiasis, and hydronephrosis, as well as the robustness of the analysis results. Inverse variance weighted results showed genetic causal relationships between BMI (P = .034, odds ratio [OR] 95% confidence interval [CI] = 1.273 [1.019–1.589]), T1D (P = .028, OR 95% CI = 0.921 [0.855–0.991]), urolithiasis (P < .001, OR 95% CI = 1.361 [1.175–1.576]), and hydronephrosis. Sensitivity analyses confirmed the accuracy and robustness of these findings. Our results support significant causal roles of BMI, T1D, and urolithiasis in hydronephrosis, potentially offering new intervention strategies for preventing its development.