Genomic and molecular characterization of preterm birth

Area of Science:

• Genomics
• Epigenetics
• Transcriptomics
• Pediatric Health

Background:

• Preterm birth (PTB) complications are a major cause of infant morbidity and mortality.
• Understanding the molecular underpinnings of PTB is crucial for developing effective interventions.

Purpose of the Study:

• To identify genomic variants and molecular signatures associated with PTB, particularly very early PTB (VEPTB).
• To integrate multi-omics data for a comprehensive understanding of PTB-related biology.

Main Methods:

• Whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation analysis of 270 PTB and 521 control families.
• Analysis of genomic variants, differentially expressed genes (DEGs), and differentially methylated loci.
• Expression and methylation quantitative trait loci (e/mQTL) analyses and pathway enrichment.

Main Results:

• Identified 160 significant genomic variants associated with PTB phenotypes, with strongest associations for VEPTB.
• Discovered 72 candidate biomarker genes for VEPTB, including previously implicated PTB genes.
• RAB31 and RBPJ were identified across all three data types (WGS, RNA-seq, methylation).
• VEPTB-associated pathways include EGFR, prolactin, inflammation, immunity, chemokine, IFN-γ, and Notch1 signaling.

Conclusions:

• Integrated multi-omics analysis, stratified by PTB subphenotype, effectively identifies molecular associations with VEPTB.
• The study provides a valuable set of candidate biomarkers and biological pathways for VEPTB.
• Further research into these identified pathways and genes can advance PTB prevention and treatment strategies.