Genetic Associations Between Gastrointestinal Diseases and Chronic Kidney Disease: An Integrated Mendelian Randomization and Bioinformatics Analysis.

INTRODUCTION: Chronic kidney disease (CKD) is a progressive condition with complex genetic and environmental influences. This study aims to investigate the genetic causal relationships between gastrointestinal diseases and CKD using the Mendelian Randomization (MR) approach and bioinformatics analysis. METHODS: We analyzed genetic associations between nineteen gastrointestinal diseases including celiac disease (CeD), inflammatory bowel disease (IBD), intestinal malabsorption, and CKD. A two- sample MR analysis was performed using publicly available Genome-Wide Association Studies (GWAS) data with SingleNucleotide Polymorphisms (SNPs) as instrumental variables (IVs). The primary analysis employed the inverse variance weighted (IVW) method, with MR-Egger and weighted median as supplements. To explore potential biological mechanisms, Functional Mapping and Annotation (FUMA) analysis was used to map genes corresponding to IVs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: Significant genetic causal effects were observed for CeD (OR = 1.021, 95% CI = 1.002-1.041, P = .032), IBD (OR = 1.051, 95% CI = 1.014-1.089, P = .006), and intestinal malabsorption (OR = 1.031, 95% CI = 1.006-1.056, P = .013) on the risk of developing CKD. Other gastrointestinal diseases did not demonstrate significant causal effects on CKD. Reverse MR analyses did not reveal significant causal effects of CKD on CeD, IBD, or intestinal malabsorption, respectively. FUMA analysis identified 93 genes associated with CeD, 143 genes with IBD, and 26 genes with intestinal malabsorption. GO and KEGG enrichment analyses highlighted key pathways, including T-cell receptor signaling, cytokine-cytokine receptor interaction, chromatin regulation, and immune-related pathways. CONCLUSIONS: This study provides genetic and bioinformatics evidence linking CeD, IBD, and intestinal malabsorption to an increased risk of CKD, highlighting the systemic impact of immune dysregulation and inflammation on kidney health.