We will identify in WP1 common and rare genetic variant mudulating the risk of ALD-HCC. We will evaluate those variants in the general population as well as NAFLD cohorts.

Our main objective is to identify novel inherited genetic variants predisposing to ALD-HCC. Those variants will be assesseld for gene-environment interactions at molecular levels in WP2 and help define risk stratification in WP3.

WP2 will evaluate how inherited genetic variants of ALD-HCC patients can be influenced by the liver environment. This will allow us to gain better insight into the onset of ALD-HCC and identify potential preventive drug targets. To increase our understanding of gene-environment intercations for the risk of ALD-HCC, we will:

• 1- Investigate the gene expression profile, nutrient/lipid metabolism and tissue anatomy in (cancerous and non-cancerous) liver tissue of ALD-HCC patients with inherited genetic variations and liver tissue of healthy people using single cell and spatal-omics approaches.
• 2-  Perform multi-omics data integration for each inherited genetic variant, identified in WP1, to identify the involvement of metabolites/lipids, specific cell types, cellular pathways and specific tissue disorganization.
• 3- Validate findings in preclinical mouse models

We will use cutting-edge technologies: single cell/nuclei RNAseq, spatial transcriptomics/metabolomics/lipidomics and histological profiling. These will provide us, with unprecedented mechanistic and conceptual detail, information on how gene-environment interactions unfold in alcohol-related liver carcinogenesis.

The main objective of this work package is to set up and coordinate efficient strategies for internal and externalcommunication in the GENIAL project, to disseminate information and train relevant stakeholders outside of the project.

Objectives:

• Identity creation, creation of dissemination infrastructure, external dissemination actions and communication
• Internal dissemination and its management
• Training
• Risks surveillance and business development strategy

In WP5, we navigate the ethical, administrative and technical complexities of GENIAL. Our first task is ensuring that our research respects all ethical considerations and the General Data Protection Regulation (GDPR). We’ll manage all aspects of the projects, from activity scheduling, quality checks, and financial coordination to contractual management and conflict resolution. Our goal is a well-organised project that meets its objectives, delivers results, and comlies with EU regulations.