The diverse clinical manifestations of hemoglobinopathies are partly attributed to the influence of genetic modifiers. Several association studies have demonstrated the role of genetic modifiers in different hemoglobinopathy phenotypes. Previous genome-wide association studies on hemoglobinopathies have provided evidence on the role of genetic variants with a strong effect on specific disease phenotypes. It is expected that many additional genetic variants exist that can modify the disease severity.
The ITHANET portal currently curates around 750 disease-modifying variants from over 370 genes/regulatory sequence/intergenic regions. However, the majority of these variants have not been validated with confirmatory or large-scale studies, while their effect size in disease severity remains unknown. In addition, phenotype definitions may vary across studies, thus further impeding the comparison and pooling of data.
INHERENT aims to study the role of genetic modifiers in hemoglobinopathies, including sickle cell disease and β-thalassemia, through large multi-ethnic genome-wide association studies.
Specific objectives include:
- Discover new modifiers for haemoglobinopathies
- Validate previously reported modifiers
- Pooling and analysis of existing data
- Standardisation of phenotypic definitions across the network to facilitate pooling and analysis of data
- Build a research resource of GWAS data on haemoglobinopathies