The largest genetic study of hyperemesis gravidarum links the condition to 10 genes and identifies GDF15 as the strongest genetic signal, according to research in Nature Genetics. The team analysed nearly 11,000 HG cases and more than 420,000 pregnancy controls and found consistent GDF15 associations across ancestry groups. The study also implicates TCF7L2, suggests no genetic ties to hCG or estrogen, and supports new therapeutic directions including a planned metformin trial.
Large Genetic Study Identifies GDF15 as Leading Cause of Severe Pregnancy Nausea
Hyperemesis gravidarum is the most extreme form of nausea and vomiting during pregnancy. | Credit: PonyWang via Getty Images
A major international genetic study links hyperemesis gravidarum (HG) — an extreme form of pregnancy nausea and vomiting — to variations in 10 genes and identifies the gene for growth differentiation factor 15 (GDF15) as the strongest candidate driving the condition.
What the Study Found
The analysis, published April 14 in Nature Genetics, compared nearly 11,000 people diagnosed with HG to more than 420,000 pregnancy controls from nine independent studies across the U.S. and Europe. Researchers found 10 genes associated with increased HG risk, with GDF15 producing the most consistent signal across ancestry groups.
GDF15 is a hormone previously implicated in appetite regulation and nausea. The team also highlighted TCF7L2, a gene known as a major risk factor for type 2 and gestational diabetes that may influence production of GLP‑1, a hormone involved in insulin signaling and appetite (and the target of drugs such as Ozempic and Wegovy).
Why This Matters
HG affects up to about 10.8% of pregnant people in severe forms that can require hospitalization and can persist throughout pregnancy. There are currently no U.S. Food and Drug Administration–approved treatments specifically for HG. Identifying genetic drivers such as GDF15 offers new avenues for diagnostic tests and targeted therapies.
Study Strengths and Limitations
The study is the largest genetic analysis of HG to date and included some non-European participants (roughly 13,000 of Asian ancestry and more than 1,200 of African ancestry), but it remained dominated by individuals of European descent. The authors report associations rather than direct proof of causation, though the strength and consistency of the GDF15 signal across datasets provides compelling indirect evidence.
"These results open promising new paths to predict, diagnose and treat HG," said study co-leader Marlena Fejzo of the Keck School of Medicine. Fejzo consults for a company developing a GDF15-directed drug and serves in voluntary roles with the Hyperemesis Education and Research (HER) Foundation, disclosures noted by the authors.
Next Steps
The research team plans a clinical trial to test whether preconception treatment with metformin — a diabetes medication that can increase circulating GDF15 — might desensitize patients to GDF15 and reduce nausea and vomiting in subsequent pregnancies. This approach is experimental and will be evaluated for safety and efficacy.
For people affected by HG, the Hyperemesis Education and Research (HER) Foundation offers resources, advocacy and support. This article is informational and not medical advice; consult a healthcare professional for personal treatment decisions.
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