Genetics of preterm delivery and its cellular mechanisms: beyond genomics discoveries

Preterm delivery is the leading cause of death in children under 5-years of age and long-term child morbidity.

The preterm delivery rate has not shown any notable reduction, partly explained by our limited understanding of the mechanisms initiating labor and pregnancy complications.Our research team has established itself as a leader in the genetics of preterm delivery by conducting large-scale collaborative studies that have revealed several insights into the relationship with other traits and the pathways affected in preterm delivery.

However, our discoveries remain associations until further mechanistic insights are obtained.

We hypothesize that many small-effect variants associated with gestational duration converge on common mechanisms related to labor initiation.This project aims to determine how much the maternal and fetal genetic effects on gestational duration converge on labor-related phenotypes.

To this end, we will conduct genome-wide association studies in diverse ancestries and determine their association with other pregnancy traits.

To dissect the cellular mechanisms of such effects, we move beyond a gene-centric view and assess the cumulative effects of genetic variants on ripening and contractility phenotypes in decidualized endometrial stromal fibroblasts.

This project will advance our knowledge of the genetic architecture and biological mechanisms of gestational duration and will have implications for predicting, preventing, and managing preterm delivery.