NHLBI TOPMed: Severe Asthma Research Program (SARP)

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.

The overall goal of the Severe Asthma Research Program (SARP) is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. Subjects with mild and moderate asthma were recruited for comparison but the program was enriched for subjects with severe asthma from multiple centers. Subjects were comprehensively phenotyped for asthma related traits including lung function, atopy, questionnaires on medical and family history, exhaled nitric oxide and health care utilization including exacerbations and symptoms. Asthma is a heterogenous disease. Cluster analysis in SARP has shown multiple subphenotypes and endotypes.

• Study Design:
  • Case Set
• Study Type:
  • Case Set
• dbGaP estimated ancestry using GRAF-pop
• Subject Sample Telemetry Report (SSTR)

Inclusion Criteria:

Cases: Physician diagnosis of asthma, age 6-80, no current smokers (less than 5-10 pack years depending on age), FEV1 bronchial reversibility (≥12%) or airway hyperresponsiveness (PC20≤16mg/ml)

Exclusion Criteria:

Other respiratory diseases (for example: CF or COPD), premature birth before 35 weeks gestation, clinically relevant or untreated gastroesophageal reflux, recurrent sinopulmonary infections or obstructive sleep apnea, cancer diagnosis in the past 5 years.

SARP was conducted in 3 phases: SARP1, SARP2 and SARP3. The first 2 phases were cross-sectional (n~1200) with emphasis on in-depth patient characterization. SARP3 (n~700) is a well characterized cohort of asthmatics who had a systemic corticosteroid induced phenotype and is being followed for 3 years.

• Primary Phenotype: Asthma
• Respiratory Function Tests

• BioProject
• PubMed
• Sequence Read Archive
• BioSample
• MeSH
• PMC

• Principal Investigator
  • Deborah A. Meyers, PhD. National Institutes of Health, Bethesda, MD, USA.
• Funding Source
  • HL109164. National Institutes of Health, Bethesda, MD, USA.