The Genetic Roots of Extreme Morning Sickness
There’s morning sickness, then there’s hyperemesis gravidarum (HG). Affecting about 2% of women, this heinous pregnancy complication causes extreme nausea and vomiting that can lead to dehydration, weight loss and even death. Like many other women’s health problems, HG was considered psychological for many years, but recent research has explored genetic causes. Now, a massive new study published in Natural genetics discovered six other genes linked to the disease.
In the largest genome-wide association study of women with HG to date, an international team of researchers examined the genomes of nearly 11,000 women with the disease of European, Asian, African and Latin American ancestry, as well as the genomes of asymptomatic women. In total, they identified 10 genes linked to HG, four of which were already known.
“As this is the largest HG study ever conducted, we were able to uncover important new details that were previously unknown,” study author Marlena Fejzo of the University of Southern California said in a statement. “The fact that we studied women from multiple ancestry groups suggests that these results might be generalizable to a broad population.”
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The strongest link discovered was to the growth differentiation factor 15 gene (GDF15). Involved in cell growth and repair, this gene controls the production of a hormone of the same name, which is expressed in most organs and increases production after injury. It is also produced by the placenta, causing GDF15 levels to skyrocket during pregnancy.
Previous research has shown that women exposed to lower levels of GDF15 before pregnancy have more severe HG symptoms than those exposed to higher levels. Researchers believe these higher levels reduce susceptibility to large increases in GDF15 during pregnancy, thereby protecting women from the disease. In the future, Fejzo and his team plan to study whether metformin, a diabetes drug that increases GDF15 levels, could be given to women before pregnancy to reduce sensitivity and prevent symptoms of HG.
And the links to diabetes don’t stop there. One of the new genes associated with HG (called TCF7L2) is also a risk factor for type 2 diabetes and gestational diabetes, and may be involved in GLP-1 activity. “This is a completely new target, and it’s not yet clear what it does during pregnancy,” Fejzo said.
Other genes linked to HG include those involved in appetite and nausea, as well as shortened pregnancy duration, preeclampsia and brain plasticity. With so many new targets to study, this study should keep researchers busy for quite a while. “Now that we have more than doubled the genes associated with HG, we can delve deeper into the biology behind this disease, as well as possible new pathways to treat it,” Fejzo said.
Hopefully one day hyperemesis gravidarum will become a relic of the past, just like the doctors who considered it a psychological disorder.
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