A Network Approach to Characterize the Role of Early Life Protein Profiles in Childhood Respiratory Diseases

The first year of life represents a dynamic period of immune development that influences the risk of respiratory diseases, such as asthma, wheeze, and respiratory infections. However, the role of protein profiles during this critical window is not well characterized. In this study, we applied weighted gene correlation network analysis (WGCNA) to derive modules of immune-mediating proteins in children at age 1 year (YR) that participated in the Vitamin D Antenatal Asthma Reduction Trial (VDAART; N=294). We used regression analysis to evaluate associations between plasma protein modules at age 1 YR and incidence of childhood respiratory diseases by age 6 YR; we then integrated metabolomic, environmental, and demographic data to further characterize related ‘omics and social and environmental determinants of health (SEDH) underlying these associations. Our analysis identified four protein modules at age 1 YR associated with incidence of childhood asthma and/or recurrent wheeze (P=0.02-0.03) and respiratory infections (P=6.3×10-9-2.9×10-6) by age 6 YR. Notably, modules demonstrated time-sensitive associations and were not recapitulated using age 6 YR protein profiles (Padj>0.05). Overall, our findings suggested protein profiles during the critical immune development window of the first year of life can predict development of childhood respiratory diseases, and demonstrated overlap across multiple outcomes.