Novel Integrative Analysis of Microbiome and Host Genetics in Childhood Asthma Research

Project Summary Childhood asthma poses a significant public health burden due to its high prevalence, associated healthcare costs, and long-term impacts on children's health and development. The human microbiome has been associated with asthma phenotypes, endotypes, and disease severity, positioning it as a potential therapeutic target for asthma prevention and control, particularly since the microbiome is inherently modifiable. We recently assembled the largest and most geographically diverse datasets containing infant nasal and gut microbiomes, along with host genetics data, from multiple birth cohorts within the NIH-funded Children’s Allergy and Asthma Data Repository (CADRE). This study presents a unique opportunity for a more thorough investigation into the impact of the microbiome and its interactions with host genetics on asthma risk. Unfortunately, the statistical and computational tools for analyzing the CADRE study are currently lacking, primarily due to the complex compositional structure of microbiome data. This proposal seeks to address critical gaps in the methodological literature by focusing on three major areas. Specifically, we aim to develop a comprehensive suite of statistical methods to: (1) detect host genome-wide associations with the infant microbiome; (2) identify genotype-microbiome interaction effects on childhood asthma; and (3) uncover the causal role of the infant microbiome in childhood asthma. These aims are grounded in rigorous prior research, underscoring the significance of the scientific questions and the limitations or absence of existing methods. We will apply these methods to the CADRE study. These methods have the potential to advance our understanding of the microbiome's role in childhood asthma and facilitate the development of new strategies for asthma treatment and control.