# Identification of shared diagnostic genes between osteoporosis and Crohn’s disease through integrated transcriptomic analysis and machine learning

**Authors:** Guirong Yi, Peng Zhou, Qinxu Yang, Maosheng Zhao, Qiaoqiao Yang, Shensong Li, Chenpo Dang

PMC · DOI: 10.3389/fgene.2025.1609915 · Frontiers in Genetics · 2025-10-07

## TL;DR

This study identifies ABO as a shared gene involved in both Crohn’s disease and osteoporosis, offering new insights for managing these conditions together.

## Contribution

The study identifies ABO as a hub co-diagnostic gene linking Crohn’s disease and osteoporosis through integrated transcriptomic and machine learning approaches.

## Key findings

- ABO was identified as a hub co-diagnostic gene with good diagnostic value for both Crohn’s disease and osteoporosis.
- ABO was found to be involved in mitochondrial matrix, chromosomal region, and ribosome pathways in both diseases.
- In vitro experiments confirmed ABO downregulation in Crohn’s and osteoporosis cell models.

## Abstract

Crohn’s disease (CD) is a chronic inflammatory bowel disease. CD-related inflammation can lead to enhanced bone resorption and destruction, thereby increasing the risk of osteoporosis (OP). This study aimed to screen the hub co-diagnostic gene of CD and OP.

The gene expression profiles of CD and OP were obtained from the GEO database to select differentially expressed genes (DEGs). Module genes were identified by weighted gene co-expression network analysis. Two machine learning algorithms were employed to screen potential shared genes, and nomograms were constructed to assess their clinical predictive value. Receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the diagnostic performance of the hub genes. Gene set enrichment analysis (GSEA) and immune infiltration analysis were performed to explore the underlying mechanisms of the hub genes in CD and OP. In vitro experiments were conducted to validate the bioinformatics results.

The result showed that a total of 8 DEGs and 15 key module genes were found to be related to both CD and OP, from which machine learning screened out 5 potential shared genes. Subsequently, ABO was identified as the hub co-diagnostic gene with good diagnostic value. GSEA results showed that ABO was involved in the mitochondrial matrix, chromosomal region, and ribosome in both CD and OP. Immune infiltration analysis found that activated CD8 T cell, effector memory CD4 T cell, and immature B cell were all significantly negatively correlated with ABO in both diseases. In vitro experiments confirmed the downregulation of ABO in CD and OP cell models.

Overall, ABO was identified as a hub co-diagnostic gene for CD and OP, providing new insights into their co-management.

## Linked entities

- **Genes:** ABO (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) [NCBI Gene 28]
- **Diseases:** Crohn’s disease (MONDO:0005011), osteoporosis (MONDO:0005298)

## Full-text entities

- **Genes:** ABO (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) [NCBI Gene 28] {aka A3GALNT, A3GALT1, GTA, GTB, NAGAT}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}
- **Diseases:** inflammation (MESH:D007249), inflammatory bowel disease (MESH:D015212), CD (MESH:D003424), OP (MESH:D010024)

## Full text

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## Figures

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## References

66 references — full list in the complete paper: https://tomesphere.com/paper/PMC12538133/full.md

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Source: https://tomesphere.com/paper/PMC12538133