Genetic Insights into Associations Between Bowel Diseases and Chronic Kidney Disease by Two-Sample Mendelian Randomization

Abstract Objective This study aims to investigate the genetic causal relationships between gastrointestinal diseases—specifically celiac disease (CeD), and inflammatory bowel disease (IBD)—and chronic kidney disease (CKD). Methods We conducted a two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) data. Two sets of single-nucleotide polymorphisms (SNPs) were chosed as instrumental variables(IVs), 32 SNPs related with CeD and 68 SNPs associated IBD. The primary analysis utilized the inverse variance weighted (IVW) method, supplemented by MR-Egger and weighted median approaches. Results Our findings indicate significant genetic causal effects of CeD and IBD on the risk of developing CKD. The IVW method showed a positive association between CeD and CKD (OR = 1.021, 95% CI = 1.002–1.041, P = 0.032), with stronger effects observed for IBD (OR = 1.051, 95% CI = 1.014–1.089, P = 0.006). Reverse MR results of CKD on CeD (P = 0.435; OR = 0.939) and CKD on IBD (P = 0.166; OR = 1.120) were not statistically significant. Conclusions The study provides genetic evidence linking gastrointestinal diseases to an increased risk of CKD. These findings highlight the importance of considering genetic predispositions when assessing CKD risk in patients with CeD and IBD.