Preeclampsia affects up to 5% of pregnancies and is first suspected when a woman is found to have high blood pressure, usually in the second half of pregnancy. Preeclampsia signs include fits, stroke, liver and blood problems; in some cases, it causes the death of mother and baby.
Preeclampsia during pregnancy has long been known to run in families; pregnant women whose mothers or sisters had preeclamptic pregnancies are more likely to also develop the condition, suggesting a genetic root. More recently, studies have found that fathering preeclamptic pregnancies runs in the families of men, too. The study put this information together, along with the third piece of the puzzle: the baby’s developing DNA.
“We knew that faulty formation of the placenta is often found in preeclampsia. As it is the baby’s genes that produce the placenta we set out to see if we could find a link between the baby’s DNA and the condition,” said Dr Linda Morgan, from the University of Nottingham’s School of Life Sciences, who coordinated the study that spanned five years and included samples from four countries. “We found there were indeed some features in a baby’s DNA that can increase the risk of preeclampsia.”
Laboratory and statistical analysis of the genetic make-up of 4,380 babies born from preeclamptic pregnancies (compared with DNA from more than 300,000 healthy individuals) pinpointed the location in the baby’s DNA that increases risk of preeclampsia during pregnancy. This location was confirmed by other InterPregGen members to fit hand-in-glove with other medical information about preeclampsia.
The baby’s DNA comes from both its mother’s and its father’s genes — in keeping with the inherited risk of preeclampsia. The DNA changes associated with the pregnancy complication are common — more than 50% of people carry this sequence in their DNA, so the inherited changes are not enough to be the sole preeclampsia causes, but they do increase the risk of preeclampsia.
It’s confirmation of a genetic risk factor for a condition that has been long known, but little understood. Preeclampsia was a recognized condition during the heydays of ancient Egypt and Greece, but “because preeclampsia has its origins in the very early stages of pregnancy, during the formation of the placenta, research into the causes and processes of the disease has always been challenging,” said Dr Ralph McGinnis, who led the analysis at the Wellcome Trust Sanger Institute in the UK. “Now modern genome wide screening and its data analysis allows us to look for clues in the mother’s, father’s and their baby’s DNA. We believe the new insights from this study could form the basis for more effective prevention and treatment of preeclampsia in the future, and improve the outcome of pregnancy for mother and child.”
Specifically, the research found DNA variations close to the gene that makes a protein called sFlt-1 with significant differences between the babies born from preeclamptic pregnancies and the control group. At high levels, sFlt-1 released from the placenta into the mother’s bloodstream can damage her blood vessels, leading to high blood pressure, and damage to her kidneys, liver and brain — all features of preeclampsia. If a baby carried these genetic variants it increased the risk of that pregnancy being preeclamptic.
DNA from a further 4,220 babies from preeclamptic pregnancies in Kazakhstan and Uzbekistan is currently being analysed in an extended study to see if the same variations occur near sFlt-1.
Iceland’s deCODE Genetics also contributed to the analysis, published in the journal Nature Genetics.