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Study Description

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 5b (GRCh38) and Freeze 8 (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 5b, Phases 1 and 2" and "TOPMed Whole Genome Sequencing Project - Freeze 8, 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.

Establishing a Brazilian Sickle Cell Disease Cohort and Identifying Molecular Determinants of Response to Transfusions, Genetic Determinants of Alloimmunization, and Risk Factors Associated with HIV Infection. The REDS-III Brazil SCD Cohort study focused on transfusion practices and predictors of health outcomes in patients with Sickle Cell Disease (SCD) and began in the Fall of 2013. The four primary aims of this study are: 1) Aim A - Establish a cohort of SCD patients with a comprehensive centralized electronic database of detailed clinical, laboratory and transfusion information, as well as establish a repository of blood samples to support biological studies relevant to SCD pathogenesis and transfusion complications; 2) Aim B - Characterize changes in markers of inflammation in response to transfusion by analyzing chemokine/cytokine panels in serial post transfusion specimens; 3) Aim C - Identify single nucleotide polymorphisms (SNPs) that contribute to the risk of red blood cell alloimmunization in SCD by performing a genome-wide association (GWA) study in transfused SCD patients; and, 4) Aim D - Characterize risk of HIV and HIV outcomes in the Brazilian SCD population and compare SCD outcomes among HIV sero-positive and sero-negative SCD patients. Patients are enrolled from six hospitals affiliated with the participating four REDS-III Brazil hemocenters.

Authorized Access
Publicly Available Data
Study Inclusion/Exclusion Criteria

Eligible participants classified as adult (≥18 years of age) and pediatric patients (<18 years) were identified by randomly selecting patients with a confirmed diagnosis of sickle cell disease and at least one clinical encounter in the last three years at the 6 REDS-III sites. Stratified random sampling was conducted proportional to the age (<18 or ≥18), gender and SCD genotype distributions of the patients at each hemocenter to ensure the study population was reflective of the SCD population at each site

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Sequencing Illumina HiSeq X Ten N/A N/A Baylor College of Medicine Human Genome Sequencing Center
Study History

This study was funded by the NHLBI in March 2013 under the Recipient Epidemiology and Donor Evaluation Study III (REDS III). Whole genome sequencing of the cohort was funded by the NHLBI under the Trans-Omics for Precision Medicine (TOPMed) Program.

Selected Publications
Diseases/Traits Related to Study (MeSH terms)
Authorized Data Access Requests
Study Attribution
  • Principal Investigator
    • Brian Custer, PhD. Blood Systems Research Institute, San Francisco, CA, USA.
  • Co-Investigators
    • Shannon Kelly, MD. Blood Systems Research Institute, San Francisco, CA, USA.
    • Ester Sabino. University of Sao Paulo, Brazil.
  • Funding Source
    • HHSN2682011. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.