Interactions Between Genetics, Air Pollution, and Preschool-Onset Childhood Asthma

/ABSTRACT Asthma is the most common chronic disease among children in the United States and is influenced by both genetic and environmental factors. Compared with White children, self-identified Black and Caribbean Hispanic children are up to three times more likely to develop childhood asthma before the age of four years (“preschool-onset asthma”). Preschool-onset asthma is associated with the highest hospitalization risk, reduced lung growth, and lower lung function. There is a critical unmet need to identify the root causes of preschool-onset asthma in minoritized children. A recent study from the CREW/ECHO consortium found that PM2.5 and NO2 averaged over the first three years of life is associated with increased odds of early-onset childhood asthma, and this association is increased among Black children. Furthermore, Black and Latinx children are exposed to more pollution from every type of emission source in the US. It is unknown how increased exposure to air pollution interacts with individual genetic risk factors to promote the development of preschool-onset asthma. This career development proposal is designed to evaluate gene-by-air pollution interactions to identify one of the root causes for increased preschool asthma incidence rates among children experiencing environmental injustice due to systemic racism. For this application, I propose the following specific aims: Aim 1: To conduct a candidate gene association study for preschool-onset asthma. Aim 2: To identify single nucleotide polymorphisms (SNPs) of preschool-onset asthma genes that interact with air pollution exposure in early life to increase asthma risk. Aim 3: To identify associations between air pollution exposure in the first year of life and the expression of preschool-onset asthma genes in nasal epithelial cells. This NIH K08 proposal is supported by an expert team of transdisciplinary mentors and collaborator with collective expertise in childhood asthma risk factors, environmental epidemiology, statistical genomics, and transcriptomics analysis. This K08 award will allow the achievement of the following training objectives: (1) Develop foundational training in genomic analyses and gene-environment interactions. (2) Increase expertise in assessing air pollution as an environmental risk (3) Obtain skills in transcriptomics analyses to investigate the association between the environment and the expression of preschool-onset asthma-related genes (4) Cultivate the professional skills to become a national and international leader in childhood asthma disparities research. The findings of this proposal will provide novel insights into the molecular mechanisms of individual-level susceptibility to air pollution among children in neighborhoods with high pollution exposure and will inform personalized asthma prevention studies among children living in high-risk environments. Project Number: 1K08HL173691-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Sima Ramratnam | Institution: UNIVERSITY OF WISCONSIN-MADISON, MADISON, WI | Award Amount: $176,220 | Activity Code: K08 | Study Section: NHLBI Mentored Clinical and Basic Science Study Section[MCBS (JA)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1K08HL17369101A1