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- Study Description
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- Data Use Certification (DUC) Agreement
- Talking Glossary of Genetic Terms
This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Two genotype call sets derived from WGS are now available, Freeze 8 (GRCh38) and Freeze 9b (GRCh38), with largely overlapping sample sets. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying documents, "TOPMed Whole Genome Sequencing Project - Freeze 8, Phases 1-4" and "TOPMed Whole Genome Sequencing Project - Freeze 9b, Phases 1-4". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.
Sickle cell disease (SCD) is characterized by the presence of sickle hemoglobin (HbS) within circulating erythrocytes resulting in hemolytic anemia, vascular occlusion, and end organ damage due to alterations in the shape and deformability of the cell membrane. The disease is inherited in an autosomal recessive pattern, and is most commonly caused by a single nucleotide substitution in the hemoglobin subunit beta (HBB) gene located on chromosome 11. Participants in this study include children with SCD treated with hydroxyurea to pharmacologically increase fetal hemoglobin (HbF) levels and reduce disease severity. Therefore, the primary phenotype of interest in this study is the change in HbF levels in response to hydroxyurea treatment. Genetic factors have been shown to influence inter-individual variation in drug response, and identification of novel genes and variants associated with clinical outcomes in SCD will be achieved through collaboration between Baylor College of Medicine, Augusta University, Columbia University Medical Center, Emory University School of Medicine and Children's Healthcare of Atlanta, and St. Jude Children's Research Hospital. The NHLBI TOPMed Program is designed to generate scientific resources to enhance understanding of fundamental biological processes that underlie heart, lung, blood and sleep disorders (HLBS). It is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment.
- Study Design:
- Case Set
- Study Type:
- Case Set
- dbGaP estimated ancestry using GRAF-pop
- Subject Sample Telemetry Report (SSTR)
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- Publicly Available Data (Public ftp)
- Study Inclusion/Exclusion Criteria
Inclusion Criteria: Pediatric patients with sickle cell anemia and history of hydroxyurea use
- Study History
The TOPMed Whole Genome Sequencing Project: Pharmacogenomics of Hydroxyurea in Sickle Cell Disease (PharmHU) is a collaboration between five medical institutions: Baylor College of Medicine, Augusta University, Columbia University Medical Center, Emory University School of Medicine and Children's Healthcare of Atlanta, and St Jude Children's Research Hospital.
- Selected publications
- Diseases/Traits Related to Study (MeSH terms)
- Primary Phenotype: Sickle Cell Anemia
- Links to Related Resources
- Authorized Data Access Requests
See research articles citing use of the data from this study
- Study Attribution
- Eric Boerwinkle, PhD. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
- Principal Investigator