Asthma is the most common chronic disorder of children, with an estimated 300 million cases worldwide and significant increases in incidence since the early 1980s. In the U.S., asthma prevalence, morbidity mortality, and drug response vary substantially among racial and ethnic groups. Over the last decade, our research has demonstrated that differential social experiences, including discrimination, neighborhood air quality, place of birth, and acculturation are associated with asthma and asthma health disparities. However, unlike genetic associations, discovering socio-environmental risk factors does not directly provide a path to genes or pathways. This major limitation impedes our understanding of asthma biology, reducing the rate of progress towards treatment and prevention. Our goal in this work is to identify the genes and pathways affected by socio-environmental exposures to improve our mechanistic understanding of asthma. This will lead to improved prevention, diagnosis, and treatment, particularly for Latinos and African Americans, who bear a disproportionate burden of this disease. We hypothesize that DNA methylation will provide the genomic bridge between socio-environmental factors and disease. Methylation, a long lasting but dynamic measure of cellular states, is highly correlated to environmental exposures and demographic characteristics, including age, sex, race/ethnicity, smoking, and ancestry. We will develop advanced statistical methods to anchor specific epigenetic loci associated with both asthma and socio-environmental factors. To execute this research program, we have assembled an interdisciplinary team with complementary expertise in socio-environmental epidemiology, asthma, genetics, epigenetics, and statistical methods. Our team will study a unique cohort of minority children and parent-child trios of Mexicans, Puerto Ricans, and African Americans, who have existing longitudinal survey and molecular based measures of socio-environmental exposures, genotypes, and RNA/DNA sequences. Results from our work will help: (i) identify new classes of therapeutic targets, different from those discovered via genetics, (ii) precisely treat patients by selecting interventions using epigenetic markers, (iii) improve risk profiling, especially for minority populations, and (iv) provide the global research community with the largest methylation dataset on minority children produced to date, with a substantially increased value due to existing clinical, socio-environmental, genetic, and functional genomic data.

Public Health Relevance

The goal of our project is to identify the genomic pathways that are altered by socio-environmental factors, including stress and experiences of discrimination, and underlie health disparities in asthma and other complex diseases. To accomplish this goal, we will assemble the world's largest multi-ethnic asthma cohort of minority children with measures of epigenetic, genetic, functional genomic, and socio-environmental risk factors. Of particular importance is ensuring we develop powerful statistical methods for analyzing these data. Achieving this goal requires expertise across many domains of knowledge including: medical and population genomics, algorithm development, and expertise in socio-environmental epidemiology.

National Institute of Health (NIH)
National Institute on Minority Health and Health Disparities (NIMHD)
High Priority, Short Term Project Award (R56)
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Special Emphasis Panel (ZRG1)
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Rajapakse, Nishadi
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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