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Genes behind Gestation Length and Preterm Delivery Identified

By Labmedica International staff writers
Posted on 21 Sep 2017
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Image: The Genome-wide Association Studies fact sheet (Photo courtesy of the National Human Genome Research Institute).
Image: The Genome-wide Association Studies fact sheet (Photo courtesy of the National Human Genome Research Institute).
Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. Preterm birth and gestational duration in general, is a complicated phenotype that is affected by both maternal and fetal genomes.

The definition of preterm birth as a dichotomous trait on the basis of a somewhat arbitrary cutoff of 37 weeks of gestation, rather than time of birth for a specified level of fetal maturity or as a continuous trait limits the interpretation of data and reduces the statistical power to detect association.

An international team of scientists working with those at the University of Gothenburg (Sweden) based a study on genetic data and information on gestation length for 43,568 women of mainly European origin. The information was made available to the team by 23andMe (Mountain View, CA, USA), 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 genome-wide association studies showed that there are four genes with a clear link to gestation length: Early B-Cell Factor 1 (EBF1), Eukaryotic Elongation Factor, Selenocysteine-TRNA Specific (EEFSEC), Angiotensin II Receptor Type 2 (AGTR2) and Wnt Family Member 4 (WNT4). Commonly occurring variants of the first three genes also appeared to have a determining influence on the likelihood of preterm birth that is delivery before 37 full weeks. Variants of a further two genes could also be associated with gestation length, which was most evident in the reference group.

Bo Jacobsson, MD, PhD, a professor of Obstetrics and a senior co-author of the study said, “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.” The study was published on September 6, 2017, in The New England Journal of Medicine.

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University of Gothenburg

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