The Real Cause of Extreme Pregnancy Nausea Is Genetic

Extreme pregnancy nausea is a complex biological response driven by a specific genetic signature affecting both the placenta and the brain.

A multi-ancestry study from the Keck School of Medicine of the University of Southern California (USC) has identified 10 genetic markers associated with severe nausea in pregnancy.

The biological basis of severe pregnancy sickness

Pregnancy is often associated with “morning sickness”, but for ~2% of pregnant individuals, the reality is far more dangerous. Hyperemesis gravidarum (HG) causes nausea and vomiting so severe that eating and drinking become nearly impossible, which can lead to malnourishment and dehydration, putting both the mother and baby at risk.

For years, medical professionals misunderstood HG, often dismissing it as a psychological issue; however, current research is dismantling this myth by uncovering the clear biological and genetic foundations of the condition.

Recent work has focused heavily on a hormone-encoding gene called GDF15, which produces a hormone that rises sharply during pregnancy. If a person has a genetic mutation that causes low levels of this hormone before they get pregnant, their body becomes hypersensitive to the sudden surge once they conceive. In contrast, those with higher pre-pregnancy exposure seem to be better protected against severe symptoms.

While GDF15 contributes to the condition, it does not tell the whole story. Previous genetic studies have been limited by small sample sizes or a lack of ancestral diversity, leaving a gap in the understanding of HG. The Keck School of Medicine team launched a new study to map the broader genetic landscape of HG. By looking beyond a single gene and using a diverse, international dataset, they aimed to identify new regulatory pathways that contribute to severe pregnancy sickness.

New genetics identified in multi-ancestry pregnancy research

The researchers conducted a genome-wide association study to find differences between 10,974 women who suffered from HG and 461,461 controls; the study included participants of European, Asian, African, and Latino ancestries.

The analysis identified 10 key genes linked to the condition. While four of these—including GDF15 and genes involved in placental development—were already known, six were entirely new discoveries.

One gene, TCF7L2, is a well-known risk factor for type 2 diabetes and is now linked to severe nausea in pregnancy. It may influence the gut hormone GLP-1 that controls blood sugar and appetite.

“This is a brand-new target, and it’s not yet clear what it’s doing in pregnancy,” said lead author Dr. Marlena Fejzo, an assistant professor at Keck School of Medicine, USC.

The study also pointed toward genes involved in brain plasticity, which is how the brain learns and adapts. The results suggested that for some, the brain might learn to associate certain foods with sickness, creating lasting aversions.

Beyond the nausea itself, Fejzo and the team found that these genetic markers correlate with other pregnancy outcomes. High genetic risk for HG was linked to shorter pregnancy lengths, lower birth weights, and preeclampsia.

Clinical implications for treating pregnancy sickness and nausea

Identifying these genes is a big step toward moving from biological discovery to clinical treatment.

“Now that we’ve more than doubled the genes associated with HG, we can dig deeper into the biology behind this condition, as well as new possible pathways for treating it,” said Fejzo.

While certain medications can help, for many patients, they can be ineffective and rarely eliminate all symptoms. With these findings, scientists now have several new targets for drug development, which could lead to a future where doctors use genetic profiles to match patients with the most effective medications.

“Because this is the largest study of HG ever conducted, we’ve been able to tease out important new details that were previously unknown,” said Fejzo. “The fact that we’ve studied women from multiple ancestry groups suggests that these results may be generalizable across a broad population.”

Fejzo and her team have recently received approval for a clinical trial using metformin, a common diabetes medication, as a potential treatment. Since metformin can increase GDF15 levels, the goal is to see if taking it before pregnancy can desensitize a person to the hormone, preventing the onset of HG.

Despite this progress, the exact function of some new genes, such as CDH9, remains unknown. Future work should focus on how these specific markers interact within the body.

Reference: Fejzo M, Wang X, Tan Q, Zöllner J, Pujol-Gualdo N, Laisk T. Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting. Nat Genet. 2026. doi: 10.1038/s41588-026-02564-4

This article is a rework of a press release issued by Keck School of Medicine of USC. Material has been edited for length and content.