Causal effects of inflammatory bowel diseases on the risk of kidney stone disease: a two-sample bidirectional mendelian randomization

• Published in: BMC urology Vol. 23; no. 1; pp. 1 - 162
• Main Authors: Zhang, Huayang, Huang, Yong, Zhang, Junyong, Su, Huiyi, Ge, Chengguo
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 12.10.2023; BioMed Central; BMC
• Subjects: Bidirectional mendelian randomization; Body mass index; Calculi; Consortia; Crohn's disease; Datasets; Epidemiology; Estimates; Genome-wide association studies; Genomes; Genomics; High density lipoprotein; Inflammatory bowel disease; Inflammatory bowel diseases; Intestine; Kidney stone disease; Kidney stones; Kidneys; Microbiota; Nephrolithiasis; Obesity; Observational studies; Ostomy; Pleiotropy; Risk factors; Sensitivity analysis; Statistical analysis; Ulcerative colitis; Urology
• ISSN: 1471-2490; 1471-2490
• DOI: 10.1186/s12894-023-01332-4

Abstract Background Existing epidemiological observational studies have suggested interesting but inconsistent clinical correlations between inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), and kidney stone disease (KSD). Herein, we implemented a two-sample bidirectional Mendelian randomization (MR) to investigate the causal relationship between IBD and KSD. Methods Data on IBD and KSD were obtained from Genome-Wide Association Studies (GWAS) summary statistics and the FinnGen consortium, respectively. Strict selection steps were used to screen for eligible instrumental SNPs. We applied inverse variance weighting (IVW) with the fix-effects model as the major method. Several sensitivity analyses were used to evaluate pleiotropy and heterogeneity. Causal relationships between IBD and KSD were explored in two opposite directions. Furthermore, we carried out multivariable MR (MVMR) to obtain the direct causal effects of IBD on KSD. Results Our results demonstrated that CD could increase the risk of KSD (IVW: OR = 1.06, 95% CI = 1.03–1.10, p  < 0.001). Similar results were found in the validation group (IVW: OR = 1.05, 95% CI = 1.01–1.08, p  = 0.013) and in the MVMR analysis. Meanwhile, no evidence of a causal association between UC and KSD was identified. The reverse MR analysis detected no causal association. Conclusions This MR study verified that CD plays a critical role in developing kidney stones and that the effect of UC on KSD needs to be further explored.