A multi-omics approach combining causal inference and in vivo validation identifies key protein drivers of alcohol-associated liver disease
By systematically integrating genetic causal inference with multi-level functional genomics, we identify and validate four causal protein drivers of ALD. Our findings unveil a novel pathogenic axis where ALD risk is governed by a balance between pro-inflammatory, matrix-remodeling myeloid cells (driven by TREML2/MMP12) and homeostatic hepatocyte functions (mediated by PLA2R1/MAX). These genetically validated targets provide critical insights into ALD pathophysiology and represent promising, mechanistically-defined avenues for therapeutic intervention.
Authors
- Liang Chu (ORCID: https://orcid.org/0000-0002-8257-7326)
- Xuan Ma (ORCID: https://orcid.org/0000-0001-6349-5598)
- Chao Yao (ORCID: https://orcid.org/0000-0002-8234-117X)
- Qingyi Zhou (ORCID: https://orcid.org/0000-0001-7355-6390)
- Xiaoli Wang (ORCID: https://orcid.org/0000-0002-6005-2529)
- Zilu Zhang (ORCID: https://orcid.org/0009-0000-2180-5957)
- Qianqian Cui (ORCID: https://orcid.org/0000-0002-6358-6569)
- Lei Zhang (ORCID: https://orcid.org/0000-0002-5305-8543)
Institutions
- Bengbu Medical College (CN)
- The Second Affiliated Hospital of Bengbu Medical College (CN)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-12-05
- DOI
- https://doi.org/10.3389/fimmu.2025.1714502
- Primary Topic
- Alcohol Consumption and Health Effects
- Type
- article
- Field-Weighted Citation Impact
- 0.00