Researchers from the Keck School of Medicine of USC announced on Apr. 14 that they have identified nine additional genes associated with hyperemesis gravidarum (HG), a severe form of pregnancy sickness. Six of these genes had not previously been linked to the condition, which affects about 2% of women and causes extreme nausea and vomiting during pregnancy.
The findings come from what is described as the largest genetic study on HG to date, involving data from nearly 11,000 women with HG and over 461,000 controls across diverse ancestries. The results were published in Nature Genetics.
"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 Marlena Fejzo, PhD, clinical assistant professor at the Center for Genetic Epidemiology at USC's Keck School of Medicine. "The fact that we've studied women from multiple ancestry groups suggests that these results may be generalizable across a broad population."
The research confirmed four previously known gene associations—GDF15; GFRAL; IGFBP7; and PGR—and identified six new ones: FSHB, TCFL72 SLITRK1, SYN3, IGSF11 and CDH9. TCF7L2 was highlighted as a gene already known for its link to type 2 diabetes and gestational diabetes but now implicated in HG as well.
Fejzo said the newly identified genes could help explain why some women experience more severe symptoms than others or point toward new treatments for HG: "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." She also noted ongoing research into how brain plasticity might contribute to food aversions during pregnancy.
Some genes linked to HG were also found to be associated with other adverse pregnancy outcomes such as shorter pregnancies or preeclampsia. Current medications like Zofran only partially relieve symptoms for about half of patients. The team has received approval to begin a clinical trial using metformin—a common diabetes medication—to see if increasing GDF15 levels before pregnancy could reduce or prevent symptoms in women prone to HG.
