Genetic Causes of Extreme Pregnancy Nausea and Vomiting

Scientists have identified a primary genetic driver behind extreme nausea and vomiting in pregnancy, a condition commonly known as hyperemesis gravidarum, offering new insight into why some pregnant individuals experience debilitating symptoms while others do not.

A large-scale multi-ancestry genome-wide association study published in Nature has pinpointed variations in the gene GDF15 as a major contributor to severe pregnancy sickness. The research, which analyzed genetic data from over 50,000 individuals across diverse populations, found that specific inherited variants linked to lower baseline levels of GDF15 protein are associated with a significantly higher risk of developing hyperemesis gravidarum.

GDF15, or growth differentiation factor 15, is a hormone produced by the placenta during pregnancy that helps regulate appetite and weight by acting on the brainstem. While elevated GDF15 levels are normally expected in pregnancy and contribute to typical mild nausea, the study revealed that individuals with certain genetic profiles start pregnancy with unusually low levels of this hormone. When the placenta then ramps up GDF15 production, the sudden relative increase triggers a strong adverse reaction in the brain, resulting in intense nausea and vomiting.

“This isn’t about high hormone levels causing sickness directly,” explained Dr. Marlena Fejzo, a geneticist at the Keck School of Medicine of USC and lead researcher on the study. “It’s about the mismatch between what the body is used to and what it suddenly experiences. If your baseline GDF15 is low due to genetics, the surge during pregnancy can feel like a shock to the system.”

The findings build on earlier work by Fejzo and colleagues, who first implicated GDF15 in pregnancy sickness in 2018. The new study confirms and expands those results using a much larger, globally diverse dataset, including participants of European, African, East Asian, and Hispanic ancestry. Six additional genetic loci were also identified that may influence GDF15 regulation or placental function, though GDF15 remains the strongest single factor.

Hyperemesis gravidarum affects up to 3% of pregnancies and can lead to weight loss, dehydration, electrolyte imbalances, and hospitalization. Unlike typical morning sickness, which usually resolves by the end of the first trimester, severe cases may persist throughout pregnancy and require medical intervention such as intravenous fluids, anti-nausea medications, or, in rare instances, tube feeding.

Current treatments are largely symptomatic and vary in effectiveness. The discovery of a clear biological mechanism opens the door to potential preventive strategies. Researchers are now exploring whether safely elevating GDF15 levels before conception—through controlled exposure or other means—could help the body adapt and reduce the risk of severe reaction.

“We’re not suggesting people try to manipulate their hormones on their own,” Fejzo cautioned. “But this understanding could one day lead to preventive protocols, similar to how we manage other pregnancy-related conditions with preconception care.”

The study also highlights the importance of considering ancestral diversity in genetic research. Earlier investigations that focused primarily on European populations had missed key variations now visible in broader datasets. By including multiple ancestries, scientists were able to distinguish between genetic signals that are truly causal and those that are merely population-specific markers.

Outside experts have praised the rigor of the work. Dr. Susan R. Bailey, a reproductive endocrinologist not involved in the study, noted that the findings shift the narrative around pregnancy sickness from a poorly understood discomfort to a condition with measurable biological roots.

“For too long, severe nausea in pregnancy has been dismissed or psychologized,” Bailey said. “This research validates what patients have reported for years—that there’s a real, physical basis for their suffering—and it opens a path toward better care.”

While the genetic link is strong, researchers emphasize that not everyone with the high-risk variants will develop hyperemesis gravidarum, and some without them still experience severe symptoms. Environmental factors, placental health, and individual sensitivity likely play contributing roles.

The National Institutes of Health and the March of Dimes have acknowledged the study’s potential to improve maternal health outcomes. Future research will focus on longitudinal tracking of at-risk individuals and clinical trials of preventive approaches.

For now, the discovery offers a long-sought explanation for a condition that has affected pregnant people across cultures and generations—one that may ultimately lead to earlier identification, better support, and more effective interventions.