Study of the Role of Genetic Modifiers in Hemoglobinopathies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30,000
- 试验地点
- 26
- 主要终点
- Genetic modifiers in haemoglobinopathies through GWAS
研究概览
简要总结
This study will investigate the role of genetic modifiers in hemoglobinopathies through a large-scale, multi-ethnic genome-wide association study (GWAS).
详细描述
Hemoglobinopathies, including sickle cell disease (SCD) and beta-thalassemia, are prevalent diseases with variable clinical manifestation and severity that are thought to be governed, in part, by genetic modifiers. Despite the identification and characterization of a few putative genetic modifiers by previous studies, these are as yet insufficient to guide treatment recommendations or risk-stratify patients reliably. Also, it is expected that many additional genetic variants exist that can modify disease and its severity. This large-scale genome-wide association study (GWAS) will utilize SNP chips to investigate the genetic profile of individuals with hemoglobinopathies, thereby addressing the challenges of previous studies related to small sample sizes and low statistical power, while promoting the participation of diverse populations worldwide. The study aims to i) discover new genetic modifiers of hemoglobinopathies, ii) validate previously reported genetic modifiers, iii) pool and analyze existing genomic data, iv) standardize phenotypic descriptions, v) develop a research resource of disease-specific data generated in INHERENT, including genomic, phenotypic, and functional data, and vi) develop risk scores that can be used for patient stratification.
The main endpoints include:
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Worldwide demography, including numbers of patients, main genotypes, and overall disease severity/burden in participating centres
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Genetic modifiers affecting clinical or laboratory phenotypes of hemoglobinopathies, including
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overall survival in SCD and/or thalassemia,
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stroke and/or decreased neurocognitive function in SCD and/or thalassemia,
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renal impairment in SCD and/or thalassemia,
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leg ulcers in SCD,
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priapism in SCD,
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mild or severe acute pain and/or chronic pain syndromes in SCD,
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pulmonary hypertension in SCD and/or thalassemia,
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hyperhemolysis in SCD and/or thalassemia,
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fetal hemoglobin levels,
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degree of ineffective erythropoiesis,
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hepatic fibrosis/cirrhosis and/or cardiac siderosis,
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Genetic modifiers affecting response to treatment, including
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response to hydroxyurea,
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response to iron chelation treatment,
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response to emerging therapeutic agents
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of an inherited hemoglobinopathy, including sickle cell disease (SCD), β-thalassemia, and α-thalassemia; all genotypes will be considered.
- •Age ≥ 2 years old at the time of the collection of the phenotypic data.
- •There will be no limits on study participants in terms of gender, ethnicity, morbidities.
排除标准
- •Patients treated with stem cell transplantation or genetic therapy.
- •Age < 2 years old at the time of the collection of the phenotypic data.
- •Patient or legal representative for minors unwilling or unable to give consent.
结局指标
主要结局
Genetic modifiers in haemoglobinopathies through GWAS
时间窗: 5 years
Number of genetic variants (SNPs) associated with disease-specific phenotypes
次要结局
未报告次要终点
研究者
Petros Kountouris, PhD
Associate Scientist, Lead of the Biomedical and Translational Informatics Group, Molecular Genetics Thalassaemia Department
Cyprus Institute of Neurology and Genetics