Genome and transcriptome profiling of spontaneous preterm birth phenotypes

• Published in: Scientific reports Vol. 12; no. 1; pp. 1003 - 10
• Main Authors: Gupta, Juhi K., Care, Angharad, Goodfellow, Laura, Alfirevic, Zarko, Müller-Myhsok, Bertram, Alfirevic, Ana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 631/553; 692/308/2056; 692/53; Adult; Biomarkers; Biomarkers - blood; Birth; Female; Fetal Membranes, Premature Rupture - blood; Fetal Membranes, Premature Rupture - diagnosis; Fetal Membranes, Premature Rupture - genetics; Forkhead Transcription Factors - genetics; Foxp3 protein; Gene Expression Profiling; Gene mapping; Genetic analysis; Genetics; Genome-Wide Association Study; Genomes; Gestation; Humanities and Social Sciences; Humans; Immune response; Inflammation; MicroRNAs; miRNA; multidisciplinary; Nerve Tissue Proteins - genetics; Phenotypes; PPAR gamma - genetics; Pregnancy; Pregnancy Outcome; Premature birth; Premature Birth - blood; Premature Birth - diagnosis; Premature Birth - genetics; Quantitative Trait Loci; Receptors, Cell Surface - genetics; Risk factors; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Transcription; Transcriptomes; Transcriptomics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-04881-0

Preterm birth (PTB) occurs before 37 weeks of gestation. Risk factors include genetics and infection/inflammation. Different mechanisms have been reported for spontaneous preterm birth (SPTB) and preterm birth following preterm premature rupture of membranes (PPROM). This study aimed to identify early pregnancy biomarkers of SPTB and PPROM from the maternal genome and transcriptome. Pregnant women were recruited at the Liverpool Women’s Hospital. Pregnancy outcomes were categorised as SPTB, PPROM (≤ 34 weeks gestation, n = 53), high-risk term (HTERM, ≥ 37 weeks, n = 126) or low-risk (no history of SPTB/PPROM) term (LTERM, ≥ 39 weeks, n = 188). Blood samples were collected at 16 and 20 weeks gestation from which, genome (UK Biobank Axiom array) and transcriptome (Clariom D Human assay) data were acquired. PLINK and R were used to perform genetic association and differential expression analyses and expression quantitative trait loci (eQTL) mapping. Several significant molecular signatures were identified across the analyses in preterm cases. Genome-wide significant SNP rs14675645 ( ASTN1 ) was associated with SPTB whereas microRNA-142 transcript and PPARG1-FOXP3 gene set were associated with PPROM at week 20 of gestation and is related to inflammation and immune response. This study has determined genomic and transcriptomic candidate biomarkers of SPTB and PPROM that require validation in diverse populations.