R01HG011411

Epigenome-Wide Variations and Socio-Environmental Exposures in African American Asthmatic Children - Abstract

Asthma is a major public health problem in the United States, affecting 11 million children. Despite advances in asthma care, African Americans (AAs) are 4 times more likely to be hospitalized and 5 times more likely to die from asthma than European Americans (EAs). Several factors could be responsible for the observed asthma racial disparities, including genetic and non-genetic factors.

While epigenetics appear to serve as a critical biological switch between genetic vulnerability and socio-environmental exposures, limited studies are available that directly map the socio-environmental exposures with asthmatic epigenome/genome information. In addition, current approaches do not leverage existing geospatial data such as environmental exposure and neighborhood socioeconomic conditions to improve asthma risk prediction.

In this proposal, we will utilize comprehensive geocoding algorithms and novel statistical methods to integrate social, clinical, environmental, genetic, and epigenetic data into a composite score for asthma risk stratification and prediction. The overall objective of this research is to conduct genome-wide methyl-seq analysis and leverage existing well-phenotyped AA pediatric asthma cohort with extensive socio-environmental exposures and ancestry-tailored multi-ethnic genotyping array (MEGA) data from Cincinnati Pediatrics Repository to accurately determine and develop ancestry-specific asthma risk stratification and prediction models.

The objective of this application is to undertake an epigenome-wide association study (EWAS), incorporating geocoded neighborhood- and individual-level socio-environmental predictors, and novel analytical strategies to create a composite risk score incorporating methylation risk score (MRS), ancestry, environmental exposures, and social characteristics to predict asthma. We will accomplish these objectives through the following specific aims:

1) Develop an ancestry-specific methylation risk score (MRS) for asthma and test its association with socio-environmental exposures contributing to asthma risk.
2) Determine the mediation effects of MRS between genetic ancestry and asthma risk.
3) Develop a multivariable risk predictive model for asthma incorporating MRS, genetic ancestry, clinical, and socio-environmental risk factors.

The proposed research is innovative because this will be the first time an MRS approach will be used to develop a population-based risk profile in asthmatics. The study will provide insights into the use of risk stratification for screening and targeted interventions. This work is significant because it can serve as a model to study the composite effect of MRS, ancestry, socio-environmental, and clinical risk factors on racial disparities in other well-documented common complex diseases beyond asthma.

Childrens Hospital Medical Center

NHGRI SUPPORTS THE DEVELOPMENT OF RESOURCES AND TECHNOLOGIES THAT WILL ACCELERATE GENOME RESEARCH AND ITS APPLICATION TO HUMAN HEALTH AND GENOMIC MEDICINE. A CRITICAL PART OF THE NHGRI MISSION CONTINUES TO BE THE STUDY OF THE ETHICAL, LEGAL AND SOCIAL IMPLICATIONS (ELSI) OF GENOME RESEARCH. NHGRI ALSO SUPPORTS THE TRAINING AND CAREER DEVELOPMENT OF INVESTIGATORS AND THE DISSEMINATION OF GENOME INFORMATION TO THE PUBLIC AND TO HEALTH PROFESSIONALS. THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM IS USED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM IS USED TO FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.172 - Human Genome Research

National Human Genome Research Institute (NHGRI) [HHS - NIH]

Cincinnati, Ohio 45229 United States

Single Zip Code

Social Epigenomics Research Focused on Minority Health and Health Disparities (R01-Clinical Trial Not Allowed) (PAR-19-372)

Amendment Since initial award the total obligations have increased 393% from $680,927 to $3,355,328.