Genetics, epigenetics, and transcriptomics of preterm birth

Abstract

Preterm birth contributes significantly to neonatal mortality and morbidity. Despite its global significance, there has only been limited progress in preventing preterm birth. Spontaneous preterm birth (sPTB) results from a wide variety of pathological processes. Although many non‐genetic risk factors influence the timing of gestation and labor, compelling evidence supports the role of substantial genetic and epigenetic influences and their interactions with the environment contributing to sPTB. To investigate a common and complex disease such as sPTB, various approaches such as genome‐wide association studies, whole‐exome sequencing, transcriptomics, and integrative approaches combining these with other ‘omics studies have been used. However, many of these studies were typically small or focused on a single ethnicity or geographic region with limited data, particularly in populations at high risk for sPTB, or lacked a robust replication. These studies found many genes involved in the inflammation and immunity‐related pathways that may affect sPTB. Recent studies also suggest the role of epigenetic modifications of gene expression by the environmental signals as a potential contributor to the risk of sPTB. Future genetic studies of sPTB should continue to consider the contributions of both maternal and fetal genomes as well as their interaction with the environment.

Maternal factors during pregnancy influencing maternal, fetal, and childhood outcomes

“…2 Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 3 University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium. 4 University of Melbourne, Melbourne, Australia.…”

“…Among the most common maternal traits that impact multiple aspects of fetal outcomes are maternal undernutrition and, more often, maternal overnutrition/obesity, associated with complications from development in an obesogenic environment and influences of gestational diabetes mellitus. In addition, the mechanisms leading to abnormalities in gestational duration and an increased risk for adverse outcomes such as preterm birth are central research targets [3]. The growing opportunity to interrogate "big data" with artificial intelligence or machine learning tools will accelerate this research and help to determine pregnancy interventions that are both safe and effective [4][5][6][7].…”

Aggregation of Genome-Wide Association Data from FinnGen and UK Biobank Replicates Multiple Risk Loci for Pregnancy Complications

“…The lead SNP, rs2963457, is located in a wide intergenic region on chromosome 5, with the closest genes, CLINT1 and EBF1 , located kbp upstream and kbp downstream of the variant consequently. The most likely causal gene in the locus is EBF1 , which has previously been implicated in PTB [ 28 ]. The rs2963457 variant identified in our analysis is in high linkage with the rs2963463 variant, previously identified as the top variant in PTB GWAS [ 13 ].…”

“…Our meta-analysis allowed us to reproduce a genome-wide association of the EBF1 locus with PTB ( Figure 2 c, Table 2 ). This locus was reported as the most significant for both PTB and gestational duration by Zhang et al [ 13 ]; and the role of EBF1 in PTB has been extensively studied [ 28 , 50 ]. EBF1 encodes a transcription factor that regulates B-cell development [ 51 ].…”

Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case–control study in China

“…Many maternal and fetal characteristics have been reported to be associated with the risk of PTB, including pregnancy spacing, multiple pregnancy, maternal chronic diseases, infection, lifestyle, undernutrition, maternal psychological health and genetic factors (8,9) . In addition, exposures to environmental chemicals, including organic pollutants, metals and metalloids, as well as air pollutants, have the potential to increase the risk of PTB through multiple pathways (10,11) .…”