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Abstract

Introduction

This study aimed to explore potential causal relationships between mitochondria-related genes and irritable bowel syndrome (IBS) using integrative multi-omics analysis.

Methods

Genome-wide association study data for IBS (1,480 cases and 454,868 controls) were integrated with mitochondrial gene data from DNA methylation quantitative trait loci, blood expression quantitative trait loci, and protein quantitative trait loci. Molecular trait associations with IBS were assessed through summary-based Mendelian randomization and co-localization analyses. Steiger filtering analysis was applied to identify causal directions, and candidate genes were independently replicated by two-sample MR in the FinnGen R11 cohort.

Results

Three primary genes supported by multi-omics evidence—, , and —were identified. Increased methylation, expression, and protein were positively associated with IBS risk, indicating pro-apoptotic and pro-inflammatory mechanisms, whereas elevated GATM expression and protein were negatively associated, consistent with a protective role creatine-mediated energy homeostasis.

Discussion

Additionally, 19 genes were classified as secondary evidence genes and 5 as tertiary evidence genes. Among these, genes such as and were validated using FinnGen data.

Conclusion

This study represents the first application of multi-omics techniques to elucidate the relationship between mitochondrial genes and IBS. The findings indicate multiple candidate pathogenic genes and highlight the role of mitochondrial dysfunction in IBS pathogenesis. These findings offer new opportunities for the discovery of IBS biomarkers and the development of therapeutic strategies.

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2025-10-29
2025-12-25

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Multi-Omics and Mendelian-Randomization Investigation of Mitochondrial Genes in Irritable Bowel Syndrome
Bentham Science Publishers ; https://doi.org/10.2174/0109298673409785250925143312
/content/journals/cmc/10.2174/0109298673409785250925143312
/content/journals/cmc/10.2174/0109298673409785250925143312
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  • Article Type:     Research Article
Keywords: mitochondrial genes ; Co-localization analysis ; mendelian randomization analysis ; IBS biomarkers ; irritable bowel syndrome ; multi-omics analysis

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