Abstract
BACKGROUND: Biological barriers are essential for maintaining integrity and function and preventing microbial invasion. Maternal barrier dysfunction may play a role in preterm birth (PTB). However, the link between maternal barrier function and PTB is still unknown. This study aims to identify genetic evidence supporting the role of maternal barrier genes in PTB risk. METHODS: We examined 201 barrier-related genes to assess their association with PTB susceptibility. We utilized the FinnGen study, published literature's whole-genome sequencing (WGS) summary statistics and Early Growth Genetics (EGG) meta-analysis to identify the maternal barrier gene associated with PTB. RESULTS: Findings from the analysis of the maternal genome highlighted several barrier genes (NOTCH1, LAMA4, F11R, MAGI1, MAGI2, TJP1, PARD3, CLDN10, CLDN14, CLDN15, GRHL3, CGNL1, LAMB2, RHOA, and LRP5) associated with PTB. Notably, NOTCH1 was supported by at least two independent genomic datasets. CONCLUSION: The established roles of NOTCH1 in vascular barrier function, angiogenesis, decidualization, intestinal epithelial barrier, and inflammation support its mechanistic involvement. Our research enhances our understanding of maternal barrier genes linked to PTB, providing valuable insights for future prevention and intervention strategies.