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

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.

Keywords: Bidirectional mendelian randomization; Crohn’s disease; Inflammatory bowel disease; Kidney stone disease; Ulcerative colitis.