Multicohort analysis unveils role for axon guidance pathways linking small for gestational age to spirometric restriction

Children born small for gestational age (SGA) are at risk for the development of metabolic, cardiovascular, respiratory, and neurodevelopmental diseases and premature mortality, but the underlying mechanisms are unknown. We analyze blood proteomic data from several birth cohorts to elucidate molecular mechanisms related to SGA and subsequent lung function outcomes in later life. We found that one-third of children born SGA manifest a distinct molecular endotype characterized by axon guidance protein dysregulation in cord blood. In later life, peripheral blood, these proteins were inversely related to concurrent spirometric restriction. We obtained orthogonal evidence from GWAS data and an experimental sheep model to show axon guidance genes are associated with spirometry measurements (FEV1/FVC) at genome-wide significance and are commonly expressed during fetal development of multiple organs. Our findings provide new insights into the developmental origins of chronic diseases and pave t..., , # Data from: Multicohort analysis unveils role for axon guidance pathways linking small for gestational age to spirometric restriction Dataset DOI: [10.5061/dryad.5mkkwh7h3](10.5061/dryad.5mkkwh7h3) ## Description of the data and file structure ### Overview This repository accompanies the publication entitled \"Multicohort analysis unveils role for axon guidance pathways linking small for gestational age to spirometric restriction\", currently being prepared for submission. It contains the data generated from the Sheep model of fetal growth restriction. ### Data #### Proteomics Proteomic data were generated with the SomaScan platform (SomaLogic, Boulder, CO, USA), which allows high-throughput, simultaneous quantification of thousands of proteins (1). The fluorescence-based detection of aptamer abundance is reported as Relative Fluorescent Units (RFU), which is proportional to the concentration in the sample. The term ‘aptamer’ refers to the short, single-stranded oligonucleotides t..., ,