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.

Methods: We applied weighted gene correlation network analysis (WGCNA) 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 (VDAART). 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 four protein modules at age 1 year associated with incidence of childhood asthma and/or recurrent wheeze (P_adj range: 0.02-0.03), respiratory infections (P_adj range: 6.3x10-9-2.9x10-6), and eczema (P_adj=0.01) 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 (P_adj range: 2.8x10-10-0.03) and alteration in metabolomic pathways (P_adj range: 2.8x10-6-0.04). No genome-wide SNPs were identified for any protein module.

Conclusion: These findings suggested protein profiles as early as age 1 year predicted development of respiratory-related diseases by age 6. In the future, 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.