Buffalo, New York: Nausea and vomiting are common during pregnancies. However, the most severe form of morning sickness, known medically as hyperemesis gravidarum or HG, can be life threatening.
Now, a large new genetic study published in the journal Nature Genetics has revealed why some women develop HG. A group of 32 researchers joined by two other teams of researchers performed a genome-wide association study (GWAS) using DNA from 10,974 women who experienced HG and compared it to DNA from 461,461 women who had normal pregnancies. The study included women of European, Asian, African, and Latino ancestries.
Scientists already knew that rising levels of certain pregnancy hormones, such as hCG (human chorionic gonadotropin) and estrogen, were often blamed for pregnancy sickness. However, this genetic study did not point to those hormones as the main cause. It highlighted specific genes.
The study found six previously unidentified genes associated with a higher risk of HG. These are: SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9. In total, the study found 10 genes linked to HG, with four previously known ones.
The strongest link was to the gene growth differentiation factor-15 (GDF15). This gene produces a hormone (also called GDF15) made by the placenta that increases a lot during pregnancy. The hormone acts on the brain’s vomiting centre and helps control appetite. The study also pointed to GFRAL, the gene that makes the receptor for this hormone in the brain. Two other genes involved in the placenta—IGFBP7 and PGR—were also associated with HG.
In the newly identified six genes linked to higher risk of HG, SLITRK1 and IGSF11 appear to affect brain pathways involved in nausea, vomiting, appetite, and signalling by brain chemicals like serotonin and dopamine. One gene, SYN3, is active in both the brain and the placenta.
What this means for treatment
HG shares some symptoms with a condition called cachexia, in which people lose weight and muscle without trying, often because they lose their appetite and feel very sick. Several of the genes linked to HG are also involved in cachexia biology.
In animal studies, researchers have been able to reduce cachexia symptoms by targeting some of these same pathways. This suggests that the genetic findings could eventually point the way toward better treatments for HG.
Right now, there is no strong genetic evidence that hCG or estrogen are the main drivers of HG. Future research will likely focus on the GDF15 pathway and the other identified genes to develop safer, more targeted therapies. More studies are still needed to fully understand how these genes work during pregnancy and to confirm the results in even larger and more diverse groups.
Arun Singh is an intern at ThePrint. He is an alumnus of ThePrint School of Journalism.
(Edited by Prashant Dixit)