A large international genetic study of hundreds of thousands of children reveals for the first time that the risk of preeclampsia, a potentially dangerous condition that can arise during pregnancy, is linked to babies’ DNA.
In the journal Nature Genetics, first author Dr. Linda Morgan, of the University of Nottingham in the United Kingdom, and colleagues report the findings of a 5-year investigation that analyzed DNA samples from children in Iceland, Norway, and Finland, and the U.K.
Preeclampsia is marked by a sudden rise in a pregnant woman’s blood pressure during the 20th week, accompanied by increased protein in her urine and swollen hands and face. It can also affect her brain, liver, and kidneys.
Preeclampsia can be fatal for both the woman and her baby, and it can also lead to long-term health complications.
The condition affects around 5 percent of pregnancies and is a leading cause of pregnancy- and birth-related deaths.
For the new investigation, Dr. Morgan and colleagues carried out a genome-wide association study (GWAS) of 4,380 children born to mothers who developed preeclampsia during pregnancy, and of 310,238 whose mothers did not develop the condition (the controls).
GWAS is a modern research method that rapidly scans the genomes or complete sets of DNA of large numbers of people to find variants in the genetic code that are linked to particular diseases.
Dr. Morgan explains that, previously, studies of preeclampsia have been difficult because the condition arises during the formation of the placenta. But now, GWAS “allows us to look for clues in the mother’s, father’s and their baby’s DNA,” she adds.
Previous GWAS analyses of preeclampsia have been done, but these have only focused on the DNA of the mothers.
Dr. Morgan says that for many years “midwives and obstetricians have known that a woman is more likely to develop preeclampsia if her mother or sister had the disorder.”
Other studies have discovered that preeclampsia “also runs in the families of men who father preeclamptic pregnancies,” she notes.
“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,” she explains.
The researchers believe theirs is the first genetic study of preeclampsia to focus on the DNA of the offspring.
The GWAS analysis – which was carried out at the Wellcome Trust Sanger Institute in Cambridge, U.K., and deCODE Genetics in Reykjavik, Iceland – identified two previously unknown DNA variants that were significantly linked to preeclampsia.
The authors note that the variants are quite common and occur in about half the population. However, they are not enough to cause preeclampsia on their own; they simply raise the risk.
The new variants are close to a gene called FLT1 that codes for a cell-surface receptor that is known to be involved in the creation of new blood vessels.
One form of FLT1 has been linked to the development of preeclampsia before. If placental levels of the associated protein become too high, they enter the pregnant woman’s bloodstream and can damage her blood vessels, resulting in high blood pressure and damage to her liver, kidneys, and brain.
Dr. Morgan summarizes the potential benefits of their findings:
“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.”
The team is now in the process of analyzing the genomes of another 4,220 babies in Kazakhstan and Uzbekistan who were born to women who had preeclamptic pregnancies to find out if they also have the same DNA variants.