Genome-wide association study shows that babies’ genetic makeup affects mothers’ risk of pre-eclampsia

A large international genome-wide association study has revealed for the first time that certain variants in a baby’s genome can increase the risk of its mother developing pre-eclampsia – a potentially dangerous condition in pregnancy.

These results from the InterPregGen study were published today in Nature Genetics. The 5-year study involved teams from the UK, Iceland, Finland, Norway, Kazakhstan and Uzbekistan and is the first to show an effect of DNA from the fetus on the health of its mother.

Pre-eclampsia 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. The condition can cause serious complications including fits, stroke, liver and blood problems and in some cases the death of mother and baby.  

Since faulty formation of the placenta is often found in pre-eclampsia and as it is the baby’s genes that produce the placenta, the researchers set out to see if they could find a link between the baby’s DNA and the condition.

The team studied the genetic make-up of 4,380 babies born from pre-eclamptic pregnancies and compared their DNA with over 300,000 healthy individuals. More than 1400 Finnish babies from the FINNPEC (Finnish Genetic of Pre-eclampsia Consortium) were included in the study.

Laboratory and statistical analysis pinpointed DNA variations close to the gene that makes a protein called sFlt-1 with significant differences between the babies born from pre-eclamptic pregnancies and the control group. If a baby carried these genetic variants it increased the risk of that pregnancy being pre-eclamptic. This result was confirmed by other InterPregGen members.

–  This gene fits hand-in-glove with other medical information about pre-eclampsia, says Dr. Hannele Laivuori from the University of Helsinki, who coordinated the study in Finland.

–  At high levels sFlt-1 released from the placenta into the mother’s bloodstream can cause damage to her blood vessels, leading to high blood pressure and damage to her kidneys, liver and brain – all features of pre-eclampsia.

The DNA changes associated with pre-eclampsia are common – over 50% of people carry this sequence in their DNA so the inherited changes are not sufficient in themselves to cause disease, but they do increase the risk of pre-eclampsia.

–  This first piece of the genetic jigsaw holds substantial promise for unlocking some of the mystery of how pre-eclampsia is caused.  We believe the new insights from this study could form the basis for more effective prevention and treatment of pre-eclampsia in the future, and improve the outcome of pregnancy for mother and child, Dr. Laivuori concludes.

The 5-year study was coordinated by University of Nottingham’s School of Life Sciences and funded by a 6 million Euro grant from the European Commission.

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Dr. Hannele Laivuori