Analysis of the Pilot Study of the International Hemoglobinopathy Research Network (INHERENT)

• Published in: Blood 2024-11, Vol.144, p.1132-1132
• Main Authors: Archer, Natasha, Stephanou, Coralea, Xenophontos, Maria, Tshilolo, Leon, Nzengu Lukusa, Franck, Fazili, Sylvain, Nnodu, Obiageli E, Nwegbu, Maxwell, Waziri, Ali Dahiru, Awwalu, Sani, Christou, Soteroula, Savvidou, Irene, Rekleiti, Ann, Minaidou, Anna, Diamantidis, Michail D, Yasin, Norafiza Mohd, Aziz, Norasmidar Abdul, Selvaratnam, Veena, Esa, Ezalia, Glenthoej, Andreas, Delicou, Sophia, Dogara, Livingstone Gayus, Dimopoulou, Maria, Sabudin, Raja, Jalil, Norunaluwar, Loh, C-Khai, Lau, Sie-Chong Doris, Zilfalil, Bin Alwi, Mohamad, Norsarwany, Mohammad, Syahiran, Ahmad-Fakri, Ahmad-Zafrullahafham, Hashim, Halim-Fikri, Oni, Morohuntodun O., Lukangu, Antonieta, Alves, Ligia, Brito, Miguel, Giannuzzi, Viviana, Bonifazi, Fedele, Michailidou, Kyriaki, Chatzimatthaiou, Sotiroula, Lederer, Carsten, Kountouris, Petros
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-200469

Background Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, represent the commonest monogenic diseases in the world, but their varying degree of clinical severity may be partly influenced by genetic modifiers. Despite the identification and characterization of several genetic modifiers by previous studies, these are, as yet, insufficient to guide treatment recommendations or stratify patients reliably. The International Hemoglobinopathy Research Network (INHERENT) will investigate the role of genetic modifiers in hemoglobinopathies, through a large, multi-ethnic genome-wide association study (GWAS), with the aim to identify and validate further disease modifiers that can be used for patient stratification and personalized treatment. Aims This pilot study aims to test the operational feasibility of the INHERENT study across different geographic and healthcare settings and, thus, identify and address challenges in performing the envisioned GWAS within INHERENT. Methods INHERENT members participating in the pilot study were selected based on their geographic location, disease group distribution (SCD/thalassemia) and hemoglobinopathy-specific healthcare policies. The following steps of study implementation were tested: (a) obtaining local bioethics approval (b) patient enrollment 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. Informed consent was obtained prior to any research activities. Results The pilot study enrolled 772 subjects from 14 centers spanning 8 countries, namely Angola, Cyprus, Denmark, DR Congo, Greece (3), Malaysia (3), Nigeria (3), and the USA. An additional thirteen centers obtained bioethics approval but have not initiated participant enrollment yet. The distribution by disease group is 52.3% SCD and 40.9% thalassemia, while the median age is 22 (mean 25.3) years, with 53.9% adult and 28.5% children (