Researchers analyzing genetic data from more than 10,000 people with hyperemesis gravidarum have identified six additional genomic regions associated with the condition, confirming several previously known links and pointing to biological pathways involved in appetite, insulin signaling and brain function.
A large multi-ancestry genetic study has identified additional genetic risk loci for hyperemesis gravidarum (HG), the severe form of nausea and vomiting in pregnancy that can lead to dehydration and hospitalization.
In the study, researchers performed a genome-wide association analysis involving 10,974 HG cases and 461,461 controls drawn from multiple ancestry groups. The research was published in Nature Genetics.
The analysis found ten genome-wide significant associations in total. Four risk genes had been implicated previously—GDF15, IGFBP7, PGR, and GFRAL—and the study reported six additional loci: SLITRK1, SYN3, IGSF11, FSHB, TCF7L2, and CDH9. Several of these signals point to pathways related to appetite regulation and metabolism (including insulin signaling) as well as brain-related processes.
The study also reinforced the central role of GDF15, a pregnancy-associated hormone that rises during gestation and has been tied in prior research to nausea and vomiting risk.
Separately, a clinical trial registered on ClinicalTrials.gov describes plans to evaluate whether metformin extended-release, taken before pregnancy, can reduce the risk and severity of HG in people who previously experienced the condition and are trying to conceive. The trial rationale is based on evidence that metformin can increase circulating GDF15, potentially reducing sensitivity to the hormone’s sharp rise during pregnancy.
