Polygenic prediction of preeclampsia and gestational hypertension

All humans have near-identical DNA sequences across the estimated 6 billion-letter code that makes up the human genome. However, slight differences exist between individuals, making each of us unique. These differences, called genomic variants, occur at specific locations within our DNA. A few genes have been shown to increase a patient’s likelihood of developing preeclampsia.

In this study, researchers used a genome wide analysis study (GWAS) method to study maternal DNA variants and preeclampsia or gestational hypertension (new onset high blood pressure without features related to preeclampsia).

The study found 18 independent loci (or genome locations) that were associated with preeclampsia/eclampsia and gestation hypertension. 12 of these loci were new (not previously identified by other genetic studies). These loci were largely comprised of genes that helped the body to develop blood vessels (angiogenesis), control blood pressure (natriuretic peptide signaling), regulate kidney function (renal glomerular function), develop the baby and the placenta (trophoblast development), and regulate the immune system (and therefore the mother’s response to being pregnant).

Why does this matter? By using a GWAS, researchers can create what is known as a genome-wide polygenic risk score. A “polygenic risk score” is one way by which people can learn about their risk of developing a disease, based on the total number of DNA changes related to the disease. A tool like this could help clinicians to assess a patient’s overall risk for developing preeclampsia. It could then help determine what patients may benefit from aspirin therapy, even among patients with first-time pregnancies (which is itself a risk factor for preeclampsia). The study looked at hundreds of thousands of women with and without preeclampsia and gestational hypertension. The researchers admitted that further studies would be needed, however, as the ancestral makeup of the patients was not wholly inclusive; around 80% were of European ancestry, ~20% were of Asian ancestry, and ~1% were of African ancestry.

Hypertensive disorders of pregnancy are known to lead to short-term risks of organ failure and long-term effects of doubled risk for cardiovascular disease. Given that “31-35% of preeclampsia predisposition has been attributed to maternal genetics”, genetic analyses to find specific loci associated with the disorder could help to predict at-risk patients.

Note: this study was supported in part by a grant from the Preeclampsia Foundation.

Take Home Message: The 18 independent loci identified by this genome wide analysis study presents new avenues of research for identifying women who may be at genetic risk of developing preeclampsia. Understanding what patients are at risk can also help to further new or previously identified treatments or prevention strategies, such as the use of aspirin. This may one day help clinicians to quickly identify those patients at most risk.

Link: https://www.nature.com/articles/s41591-023-02374-9

Citation: Honigberg, M.C., Truong, B., Khan, R.R. et al. Polygenic prediction of preeclampsia and gestational hypertension. Nat Med 29, 1540–1549 (2023). https://doi.org/10.1038/s41591-023-02374-9

ABOUT RESEARCH ROUNDUP

Each quarter, our team of science writers reviews the most current research studies related to hypertensive disorders of pregnancy and summarizes those studies of greatest interest and potential impact to our community, including research studies related to risk assessment, diagnosis, prevention, and treatment. Special thanks to our volunteer research team, who under the leadership of Dr. Elizabeth Sutton, make Research Roundup possible, and to our Patient Advisory Council, who reviews these materials from the patient perspective.