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Genes behind gestation length and preterm delivery identified

News: Sep 07, 2017

The genes that regulate gestational length and the likelihood of preterm delivery, have been identified in a study involving more than 50,000 women. An article in the New England Journal of Medicine (NEJM) describes the scientific breakthrough that can lead to improved health and survival among children.

“Preterm delivery is the leading cause of death and disease among children in the world today. Our findings will be the first step to develop better pharmacological drugs to prevent preterm delivery, and, on the other hand, also develop new drugs to induce delivery when needed," says Bo Jacobsson, professor of obstetrics and gynecology at the Department of Clinical Sciences at Sahlgrenska Academy.

He is senior researcher of the paper together with Professor Louis Muglia from University of Cincinnati. There are several other research groups from both US and Europe that have contributed to these findings.

“There are many of us research teams that have investigated this previously without finding anything. We needed these really high numbers for it to work,” says Bo Jacobsson.

Critical genes

The study is based on genetic data and information on gestation length for 43,568 women of mainly European origin. The information was made available to the researchers by 23andMe, one of the world’s largest players in DNA testing for personal use. The company’s tests are based on submitted saliva samples. Female participants who had given birth also had to state how long their pregnancies had been.

The reference group consists of 8,643 women in Denmark, Finland and Norway. The information on them comes from traditional health registers. A crucial factor in this study was the combination of a very large group, and a register-based group for which the results could be replicated.

The study shows that there are four genes with a clear link to gestation length: EBF1, EEFSEC, AGTR2 and WNT4. Commonly occurring variants of the first three genes also appeared to have a determining influence on the likelihood of preterm birth, i.e. delivery before 37 full weeks.

It has not previously been possible to clarify that these genes have these functions. It was known, however, that they are involved in governing womb development, the supply of nutrients to the fetus and control of blood circulation.

Variants of a further two genes, ADCY5 and RAP2C, could also be associated with gestation length, which was most evident in the reference group.

“All of these individually affect the risk of giving birth too soon or having an extended pregnancy. But there is nothing wrong with these genes; they are normal variants rather than mutations,” says Bo Jacobsson.

A new window

A human delivery is considerably more difficult than births of other mammals, since a full-term fetus can barely pass through a woman’s pelvis. In a female chimpanzee, for example, the passage is twice the size of the young.

Studying pregnancies by means of animal models therefore has its limitations. At the same time, knowledge of what has an impact on gestation length is of great significance. Genetics are estimated to account for between 30 and 40 per cent of the effect. According to Bo Jacobsson, it cannot be ruled out that the fetus’s genes also play a role, but it is still the mother’s genes that determine the issue.

“Our findings open up a window on better understanding of how human gestation length is governed and why labor might start too soon. It’s less about predicting who will end up in one situation or the other; now we need to move to the lab bench and conduct some studies into how this works together with various environmental factors, for example. Both we and Cincinnati have a few of these on the way,” says Bo Jacobsson.

Title: Genetic Associations with Gestational Duration and Spontaneous Preterm Birth

Contact: Bo Jacobsson

Portrait: Paulina Jacobsson

BY:

Originally published on: sahlgrenska.gu.se

Contact Information

Dept. of Obstetrics and Gynecology

Sahlgrenska University Hospital,, Östra, SE 416 85 Gothenburg

Visiting Address:
Journalvägen 6

Phone:
46-31-343 4216

Page Manager: Katarina Olinder Eriksson|Last update: 5/31/2016
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Utskriftsdatum: 2017-09-23