The activities of INHERENT are divided into five Working Groups:

Lead: Natasha Archer. Advisors: Obiageli Nnodu, Bin Alwi Zilfalil, Baba Inusa 

The Clinical WG has defined the main clinical questions to be studied by INHERENT. This includes a detailed specification of the core data parameters required for any member participation and the data parameters needed for each clinical question. The group has also developed a Case Report Form that can be used to gather data across countries with different resource capabilities. In collaboration with the Data Management and Analysis WG, finally has established clinical, laboratory and disease ontologies, such as HPO, LOINC and SCDO, that will be used for the standardization of the data, thus allowing data interoperability. 

Lead: Coralea Stephanou

This WG has developed common protocols for the GWAS experiments and for genotyping the alpha and beta globin gene clusters. The WG has agreed on the most suitable SNP array to be universally used across the network, while it is also investigating the need and feasibility of a custom content development. Moreover, the group has selected an expert genotyping center that carries out the genotyping experiments, thus ensuring consistency of GWAS experiments across the network. Finally, the group has developed all necessary protocols for the collection and transfer of samples required for the experiments.

Lead: Kyriaki Michailidou, Petros Kountouris

This WG has developed the protocols for data management, security, and analysis, including bioinformatics and biostatistics analysis, and had built the infrastructure for collecting, storing, and sharing the INHERENT data. It has collaborated with registries like RADeep and SPARCO to integrate the INHERENT CRF with these international registries in order to ensure integration, harmonization and avoidance of duplication of work. It has also created a central REDCap system for members outside existing registries. In collaboration with the Ethics WG, it has also chosen the pseudonymization solution for the INHERENT data.

A multi-ethnic GWAS study has been performed as part of the network pilot study to support the search for genetic modifiers. After quality control, data will be imputed to the latest multi-ethnic reference panel. Statistical analyses, such as survival, linear, or logistic regression, will evaluate variant effects, adjusting for confounders and selection bias. Identified modifiers will inform polygenic risk scores to improve risk estimation for various complications.

Lead: Fedele Bonifazi, Viviana Giannuzzi

This WG has mapped the existing legislation and requirements related to clinical research, personal data protection, biosample management, data/sample sharing, patient consent and assent in the participating countries and regions. Network-specific guidelines and templates were developed to coordinate and facilitate members with the applications of the research study to the competent ethics committees/Institutional Review Boards.

Lead: Kevin Kuo, Emmanuel Peprah

This WG focuses on translating knowledge from INHERENT to improve the health and wellbeing of patients with hemoglobinopathies. Through networking and close engagement with disease stakeholders, it seeks to apply INHERENT results to inform health policies, programmes, and practices locally and globally. Using an integrated KT approach, the WG works to embed INHERENT findings into the broader body of knowledge on hemoglobinopathies through quantitative and qualitative methods such as consensus conferences, expert panels, and practice guidelines. It also tailors messages to target audiences through activities like educational sessions for patients, practitioners, and policymakers, tool development, and media outreach. Additionally, the WG facilitates interaction between INHERENT researchers and decision-makers worldwide to plan, produce, disseminate, and apply findings in policy and practice.