Cross-tissue multi-omic predictors of allergic disease development and progression in early life

The National Institute of Allergy and Infectious Diseases awarded a $1.625 million Cooperative Agreement to The University of Chicago on June 9, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct a nested case-control study of food allergy, atopic dermatitis, and wheezing illness in early childhood using cross-tissue multi-omic analysis.

The recipient will characterize transcriptional and methylome signatures in blood cells and nasal mucosal cells collected from 895 children in the Systems Biology of Early Atopy (SUNBEAM) birth cohort—610 cases with food allergy, atopic dermatitis, and/or wheezing illness and 285 unaffected controls—at multiple timepoints across the first two years of life. The study addresses impaired barrier function and type 2 inflammation as shared mechanisms underlying the development and co-occurrence of these allergic diseases, which collectively affect over twenty percent of young children and account for more than twenty billion dollars in annual U.S. healthcare costs. The research will define multi-omic signatures of immune and barrier function development and their impact on atopic outcomes, testing the hypothesis that early-life exposures and genetic variation remodel the epigenetic landscape to establish developmental trajectories promoting health or disease through gene networks underlying specific disease endotypes.

Performance occurs in Chicago, Illinois through May 31, 2031.

Abstract

Food allergy (FA), atopic dermatitis (ad), and wheezing illness (WI) affect over 20% of young children, account for more than $20 billion dollars in health care costs annually in the U.S., and significantly impact quality of life. These conditions often manifest in the first year of life and often CO-occur. Impaired barrier function may be a primary causal mechanism shared by these conditions, through the development of sensitization to allergens and subsequent chronic type 2 (T2) inflammation. Yet, the genetic, epigenetic, and transcriptional mechanisms underlying predisposition and progression to these conditions, why some children develop only one condition while others develop combinations of allergic diseases, and the temporal development of each are incompletely understood. We propose to address this GAP by studying blood and nasal mucosal cells collected in children from the systems biology of early atopy (sunbeam) birth cohort, which consists of geographically and ancestrally diverse children. Sunbeam is one of very few birth cohorts with well phenotyped FA and ad outcomes. We propose a nested case-control study of study FA, ad, and WI as primary outcomes in 895 of these children (610 cases with FA, ad, and/or WI; 285 unaffected controls) and define 'omic signatures of immune and barrier function development in the first year of life and their impact on atopic outcomes to 2 years of age. Our central hypothesis is that early life exposures and genetic variation remodel the epigenetic landscape during the first year of life to establish developmental trajectories that promote health or disease states by modulating expression of gene networks underlying specific endotypes of allergic diseases. In aim 1, we will characterize transcriptional and methylome signatures (combined and individually) in blood cells and in nasal mucosal cells collected at 2, 5, and 12 months of age and build prediction models for the development of FA, ad, and/or WI by 24 months. In aim 2, we will consider main and interaction effects of prenatal (maternal) and first year (infant) exposures on the development of 'omic signatures and on clinical outcomes. In aim 3, we will identify quantitative trait loci (qtls) for expressed genes (eqtls) and methylated cpgs (meqtls) that are members of the prediction models in blood or nasal mucosal cells and will then colocalize the qtls with variants from published genome-wide association studies (gwas) of allergic traits. The sunbeam birth cohort affords an extraordinary opportunity to characterize (i) the molecular changes that occur in the first year of life, (II) the impact of exposures on these changes, and (III) their role in allergic disease onset and progression. Our proposed studies to build 'omic predictors of risk in early life that reflect the shared and distinct etiologic pathways underlying these conditions have the potential to significantly impact the public health and personal burdens imposed by these diseases. In the end, these studies may suggest new personalized prevention strategies and treatments for these common, devastating conditions.