ArticleAmerican journal of translational research2025
A set of downregulated pleiotropic genes are possible multi-omics biomarkers underlying the irritable bowel syndrome-non-alcoholic fatty liver disease comorbidity.
Article in American journal of translational research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo investigate the genetic relationship between irritable bowel syndrome (IBS) and non-alcoholic fatty liver disease (NAFLD).
methodsMendelian randomization (MR) was used to assess causality between IBS and NAFLD in a genome-wide association study (GWAS) data. Genetic correlation was evaluated by linkage disequilibrium score regression (LDSC). Shared loci were identified using PLACO, coloc, and MAGMA for pleiotropic gene mapping. Functional enrichment (Gene Ontology [GO]/Kyoto Encyclopedia of Genes and Genomes [KEGG]) was performed. Single-cell RNA-sequencing of NAFLD liver samples was used to assess gene dysregulation and calculate activation scores. Mouse models were used to validate gene expression. The identified pleiotropic gene set and their dysregulation signatures provide a foundational resource for future development of predictive multi-omics biomarkers.
resultsMR revealed a significant causal effect of IBS on NAFLD risk (Inverse-variance weighted: OR = 1.118, 95% CI = 1.03-1.21, P = 0.006; Steiger P < 0.05). Significant genetic correlation was observed (LDSC P < 0.05). Analyses identified 194 pleiotropic SNPs, mapping to 12 genes (e.g.,
conclusionsIBS exhibits a unidirectional causal effect on NAFLD, and there is a significant genetic association between them. The collective downregulation of shared pleiotropic genes (
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