Genome and transcriptome profiling of spontaneous preterm birth phenotypes

Area of Science:

• Genomics and Transcriptomics
• Maternal-Fetal Medicine
• Biomarker Discovery

Background:

• Preterm birth (PTB) before 37 weeks gestation is a major obstetric complication.
• Spontaneous preterm birth (SPTB) and preterm premature rupture of membranes (PPROM) have distinct underlying mechanisms.
• Identifying early pregnancy biomarkers is crucial for predicting and managing PTB.

Purpose of the Study:

• To identify maternal genomic and transcriptomic biomarkers for SPTB and PPROM in early pregnancy.
• To investigate molecular signatures associated with different PTB subtypes.
• To establish candidate biomarkers for risk stratification of PTB.

Main Methods:

• Recruitment of pregnant women and categorization of pregnancy outcomes (SPTB, PPROM, HTERM, LTERM).
• Collection of maternal blood samples at 16 and 20 weeks gestation.
• Genome-wide genotyping (UK Biobank Axiom array) and whole-transcriptome analysis (Clariom D Human assay).
• Genetic association, differential expression, and eQTL analyses using PLINK and R.

Main Results:

• A genome-wide significant SNP (rs14675645 in ASTN1) was associated with SPTB.
• MicroRNA-142 and the PPARG1-FOXP3 gene set were associated with PPROM, linked to inflammation and immune response.
• Several significant molecular signatures were identified in preterm birth cases.

Conclusions:

• Candidate genomic and transcriptomic biomarkers for SPTB and PPROM have been identified.
• These biomarkers, particularly those related to inflammation for PPROM, warrant further investigation.
• Validation in diverse populations is necessary to confirm the clinical utility of these findings.