Network analysis reveals protein modules associated with childhood respiratory diseases

Abstract

Background

The first year of life represents a dynamic immune development period that impacts the risk of developing respiratory-related diseases, including asthma, recurrent infections, and eczema. However, the role of immune-mediating proteins in childhood respiratory diseases is not well characterized in early life.

Objective

The objective of this study was to investigate relationships between protein profiles at age 1 year and respiratory-related diseases by age 6 years, including asthma, recurrent wheeze, respiratory infections, and eczema.

Methods

We applied weighted gene correlation network analysis to derive modules of highly correlated proteins during early life immune development using plasma samples collected from children at age 1 year (n = 294) in the Vitamin D Antenatal Asthma Reduction Trial. Using regression analysis, we evaluated relationships between protein modules at age 1 and respiratory-related diseases by age 6. We integrated protein modules with additional omics and social, demographic, and environmental data for further characterization.

Results

Our analysis identified 4 protein modules at age 1 year associated with incidence of childhood asthma and/or recurrent wheeze (adjusted Ps = .02 to .03), respiratory infections (adjusted Ps = 6.3 × 10⁻⁹ to 2.9 × 10⁻⁶), and eczema (adjusted P = .01) by age 6 years; associations between modules and clinical outcomes were temporally sensitive and were not recapitulated using protein profiles at age 6 years. Age 1 modules were associated with environmental factors (adjusted Ps = 2.8 × 10⁻¹⁰ to .03) and alterations in metabolomic pathways (adjusted Ps = 2.8 × 10⁻⁶ to .04). No genome-wide single nucleotide polymorphisms were identified for any protein module.

Conclusion

These findings suggested that protein profiles at age 1 year predicted development of respiratory-related diseases by age 6. Applying network approaches to study protein profiles may represent a new strategy to identify children susceptible to respiratory-related diseases in the first year of life.