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Analysis of the pilot study of the International Hemoglobinopathy Research Network (INHERENT)

2025-10Póster em conferência Acesso aberto
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datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorKountouris, Petros
dc.contributor.authorStephanou, Coralea
dc.contributor.authorXenophontos, Maria
dc.contributor.authorMinaidou, Anna
dc.contributor.authorChristou, Sotiroula
dc.contributor.authorSavvidou, Iren
dc.contributor.authorRekleiti, Anna
dc.contributor.authorPyrovolaki, Katerina
dc.contributor.authorConstantinou, Natasa
dc.contributor.authorTshilolo, Leon
dc.contributor.authorNzengu, F.
dc.contributor.authorFazili, S.
dc.contributor.authorBrito, Miguel
dc.date.accessioned2026-04-20T10:49:47Z
dc.date.available2026-04-20T10:49:47Z
dc.date.issued2025-10
dc.description.abstractIntroduction: Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, represent the commonest monogenic diseases. Although their pathogenesis is well established, the diverse clinical manifestations and their varying degree of severity are less understood and are partly influenced by genetic modifiers. Despite the identification and characterization of genetic modifiers by previous studies, these are, as yet, insufficient to guide treatment recommendations or stratify patients reliably. The International Hemoglobinopathy Research Network (INHERENT) investigates the role of genetic modifiers in hemoglobinopathies, intending to identify and validate further disease modifiers. This pilot study tested the operational feasibility of the INHERENT study across different geographic and healthcare settings and identified and addressed challenges in performing a large, multi-ethnic genome-wide association study (GWAS). Methods: The following steps of the study implementation have been tested: (a) obtaining local bioethics approval based on the applicable local legal framework, (b) patient enrolment, written informed consent, and data collection using a common case report form (CRF), (c) sample collection and shipment, (d) genotyping of globin genes, (e) centralized GWAS experiments, and (f) statistical analysis. The completeness of the collected dataset was also assessed. Results: The pilot study enrolled 1044 patients from 15 centres spanning 8 countries, namely Angola, Cyprus (2), Denmark, DR Congo, Greece (3), Malaysia (3), Nigeria (3), and the USA. An additional 13 centres have obtained bioethics approval, but have not initiated patient enrolment yet. The distribution by disease group is 42.2% SCD and 57.8% thalassemia patients, while the median age is 28 years (mean: 31.1), with 69.6% adult and 30.4% pediatric patients. Data completeness (affirming presence, absence, or not enough data) of key parameters related to medical complications is approximately 85%, while the range of completeness for laboratory parameters was wide, with a maximum at 80%. Notably, a higher rate of cardiac/pulmonary, kidney/liver, endocrinological, and bone complications is observed in adult thalassemia patients, while a higher rate of pain-related and acute anemia complications is observed in pediatric SCD patients. Biological material for 768 of the patients was shared centrally, and GWAS experiments have been performed using the Illumina GSA SNP array. Key challenges identified in the pilot study include: a) the unavailability of key phenotypic data in routine clinical practice in several countries, particularly when the tests are not covered by insurance; b) the need for a more detailed standardization and simplification of the INHERENT CRF to ensure uniform and consistent collection of data across participating centers; c) the unavailability, limited access or high costs of molecular diagnosis services in some countries; d) varying levels of knowledge and technical skills in laboratory work across centers; e) challenges related to the storage, quality and shipping of biological material in some countries. Conclusion: The pilot study tested common standards developed within INHERENT and enabled early identification of key challenges associated with the execution of a large, multi-ethnic study for hemoglobinopathies. The pilot is pivotal for scaling up the INHERENT GWAS across the entire network, enabling the study of a hemoglobinopathy population of unprecedented size and diversity.eng
dc.identifier.citationKountouris P, Stephanou C, Xenophontos M, Minaidou A, Christou S, Brito M, et al. Analysis of the pilot study of the International Hemoglobinopathy Research Network (INHERENT). In: 20th Annual Sickle Cell & Thalassaemia Conference, London (UK), October 1-4, 2025. British Journal of Haematology. 2025;207 Suppl 1:S98-9.
dc.identifier.urihttp://hdl.handle.net/10400.21/22807
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.relation.hasversionhttps://onlinelibrary.wiley.com/toc/13652141/2025/207/S1
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectHemoglobinopathy
dc.subjectInternational Hemoglobinopathy Research Network
dc.subjectINHERENT
dc.titleAnalysis of the pilot study of the International Hemoglobinopathy Research Network (INHERENT)eng
dc.typeconference poster
dspace.entity.typePublication
oaire.citation.conferenceDate2025-10
oaire.citation.conferencePlaceLondres, Reino Unido
oaire.citation.endPageS99
oaire.citation.issueSuppl 1
oaire.citation.startPageS98
oaire.citation.titleBritish Journal of Haematology
oaire.citation.volume207
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameBrito
person.givenNameMiguel
person.identifier.ciencia-id231F-F341-7E93
person.identifier.orcid0000-0001-6394-658X
person.identifier.ridA-7970-2016
person.identifier.scopus-author-id35224551000
relation.isAuthorOfPublication4252d8e0-800c-4d67-8b13-0b711d860669
relation.isAuthorOfPublication.latestForDiscovery4252d8e0-800c-4d67-8b13-0b711d860669

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