NHLBI TOPMed: The Genetics and Epidemiology of Asthma in Barbados

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.

Asthma is a complex disease where the interplay between genetic factors and environmental exposures influences susceptibility and disease prognosis. Asthmatics of African descent tend to have more severe asthma and more severe clinical symptoms than individuals of European ancestry. The baseline prevalence of asthma in Barbados is high (~20%), and from admixture analyses, we have determined that the proportion of African ancestry among Barbadian founders is similar to U.S. African Americans, rendering this a unique population to disentangle the genetic basis for asthma disparities among African ancestry populations in general. We therefore performed whole genome sequencing on 1,100 individuals from the Barbados Genetics of Asthma Study (BAGS), in order to generate additional discovery of rare and structural variants that may control risk to asthma.

• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Family
• dbGaP estimated ancestry using GRAF-pop
• Subject Sample Telemetry Report (SSTR)

Subjects were prioritized for sequencing based on family membership, and subjects having blood samples with sufficient quantity and quality of DNA. 1100 individuals from 190 Barbados families were whole genome sequenced (asthma cases and controls). Among all cases, asthma was defined as both a reported history of asthma and a documented history of physician-diagnosed asthma (past or current). For each of the asthma studies, a standardized questionnaire based on either American Thoracic Society or International Study of Asthma and Allergy in Childhood questionnaires was administered by a clinical coordinator. The identity and relationships of individuals were checked using IBD estimates, and individuals were excluded if discrepant. Samples that failed whole genome sequencing quality control were also excluded.

Epidemiologic studies of asthma have been underway in Barbados since 1991, when PI Barnes reported a relationship between modernization of the domestic environment in Barbados and increased risk of asthma. The baseline prevalence of asthma in Barbados is high (~20%), and from admixture analyses, we have determined that the proportion of African ancestry among Barbadian founders is similar to U.S. African Americans, rendering this a unique population to disentangle the genetic basis for asthma disparities among African ancestry populations in general. The primary outcome measure is asthma, and the approach for characterizing asthma in the Barbados population is based on the validated Respiratory Health Questionnaire (RHQ) designed from the 1978 American Thoracic Society questionnaire. Additional phenotype data include lung function measures, asthma severity, total serum IgE, and serum levels of various cytokines. In 1993, the Barbados Asthma Genetics Study (BAGS) was initiated on nuclear and extended asthmatic families who self-reported as African Caribbean, resulting in the first evidence for linkage for asthma and tIgE in an African-ancestry population, and the development of novel family-based methods. Recruitment into the BAGS program was enhanced through its involvement in the international Genetics of Asthma International Network (1999-2001) and the current sample of >1300 participants continues to grow through the efforts of collaborators and nursing staff at the Chronic Disease Research Centre in Barbados. Pediatric probands were recruited through referrals at local polyclinics or the Accident and Emergency Department at the Queen Elizabeth Hospital, and their nuclear and extended family members were subsequently recruited. All subjects gave verbal and written consent as approved by the Johns Hopkins Institutional Review Board (IRB) and the Barbados Ministry of Health.

• Primary Phenotype: Asthma

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

• Principal Investigator
  • Kathleen Barnes, PhD. University of Colorado, Denver, CO, USA.
• Funding Sources
  • R01 HL104608-S1. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.