On 24 August at 12:00 Triin Kikas will defend her doctoral thesis “Single nucleotide variants affecting placental gene expression and pregnancy outcome”.
Professor Maris Laan, University of Tartu
Associate Professor Kristiina Rull, University of Tartu
Professor D. Stephen Charnock-Jones, University of Cambridge (UK)
The placenta is a unique transient organ only present during the pregnancy. Deviations from normal placental development can lead to pregnancy complications such as preeclampsia. One of the risk factors for complications is a disruption of important placental gene expression profiles. Mechanisms that regulate the placental genes to provide accurate and dynamic expression in response to fetal needs and pregnancy stage are still not fully understood. Genetic variants modulating gene expression or eVariants are among many possible mechanisms. Still, placental eVariants are underexplored.
This thesis project aimed to investigate the effect of placental variants on gene expression and the risk of developing a pregnancy complication. First, the variation near two preeclampsia candidate genes, Vascular endothelial growth factor receptor 1 (FLT1) and stanniocalcin-1 (STC1) were analyzed. I detected a specific association between preeclampsia risk and a FLT1 variant in a sizeable Estonian cohort (2097 pregnant women). Interestingly, the preeclampsia risk variant affected FLT1 gene expression only in the preeclampsia placentas. Another variant near STC1 was shown to affect the gene expression, but its link to preeclampsia risk needs further research. Secondly, I conducted a genome-wide analysis to identify placental eVariants broadly. Overall, I uncovered 199 links that affected the expression of 63 genes, 13 of which were previously unknown for the placenta. Illustrating the broad impact of placental genetic variants, some eVariants were previously associated with adult diseases or pointed to an association with newborn parameters in the analyzed sample set. Combining the results with previous studies, I compiled a list of over 400 robust placental genes affected by genetic variation. This overview is a good starting point for future placenta eVariant research both in biological and medical aspects, e.g., regarding pregnancy complications.