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Researchers find genetic associations for morning sickness

Researchers have found genetic associations for morning sickness, offering important insight into what — in the most severe cases — is the second leading cause of hospitalization among women during pregnancy.

Although morning sickness is very common — up to 90 percent of women have some form of nausea or vomiting during pregnancy — its causes remain elusive. Up to 2 percent of pregnant women endure the most severe form of morning sickness, called hyperemesis gravidarum or HG. HG can be so serious and intractable that women begin losing weight, become dehydrated, and ultimately must be hospitalized. In those cases, the condition can also be problematic for the baby.

Before the advent of intravenous hydration in the 1950s, HG was the leading cause of death during pregnancy — for example, it led to the death of author Charlotte Bronte. More recently Kate Middleton, Duchess of Cambridge, was hospitalized after suffering from HG during both of her pregnancies. Even now it is the second leading cause of hospitalization for pregnant women behind preterm labor. And yet despite years of study, researchers haven’t pinpointed a cause, or even a safe and effective treatment for this severe form of morning sickness.

But a new study published in the journal Nature Communications offers promising clues on the causes of morning sickness. Researchers from UCLA, USC and 23andMe, found the strongest genetic associations in the genes GDF15 and IGFBP7. GDF15 plays a role in the development of the placenta, and low expression of GDF15 is associated with miscarriages. The gene IGFBP7 controls appetite.  The study also looked at less severe cases of morning sickness and found that these same genes are also associated with nausea and vomiting in pregnant women.

Researchers said that the variants in GDF15 associated with the condition were over 1000-fold more significant than the variants in the gene with the next closest association. The findings are surprising, in part, because up until now much of the focus of research around HG has been on hormonal fluctuations in the body. This study found no evidence for that link, and instead suggests that the expression of the gene involved in placenta formation may play more of a role.

“It has long been assumed that the pregnancy hormones, human chorionic gonadotropin or estrogen, were the likely culprits of extreme nausea and vomiting, but our study found no evidence to support this,” said Marlena Fejzo, the lead author of the study and an associate researcher at the David Geffen School of Medicine at UCLA.  Fejzo herself had hyperemesis gravidarum and lost a pregnancy to the condition in 1999.

The two genes identified in the study are also linked to cachexia, a weight loss and muscle wasting condition that leads to death in about 20 percent of cancer patients and has similar symptoms to hyperemesis gravidarum.

As for why the expression of GDF15 is implicated in morning sickness, the authors theorize that perhaps the protein triggers vomiting during the early stages of pregnancy so women aren’t tempted to eat anything that might hurt the developing fetus.

For this study researchers conducted their work in two stages. The first used about 1,300 women with the most severe form of morning sickness and another 15,700 who did not have the condition. All the women were 23andMe customers who consented to participate in research. The second stage looked at data from more than 50,000 women — also 23andMe customers who consented to participate in research — across a range of symptoms from no nausea to slight to very severe. Again, the researchers found the strongest signal in the genes GDF15 and IGFBP7.

 

The study also provides the first evidence that HG, the most severe form of morning sickness, is not a separate disease, but more of an end of the spectrum for nausea and vomiting during pregnancy, as they are all influenced by the same genes.

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