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.

Keywords: GWAS; RNA-seq; WES; environment; epigenome; genes; genome; gestation; inflammation; spontaneous; transcriptome.

Figure 1:. Causes and interaction among various factors leading to preterm birth.

Preterm birth is a result of various factors, many of which overlap, resulting in the common outcome of preterm delivery. Several genes associated with inflammation and infection have been implicated with preterm birth. Many of the environmental factors likely lead to genetic and epigenetic changes resulting in preterm birth.