References to previously published work in the summary below are given as PubMed IDs.
Nausea and vomiting during pregnancy (NVP) is estimated to occur in around 70% of women globally, with 1.1% of women estimated to experience severe cases, diagnosed as Hyperemesis Gravidarum (HG) (PMID: 23863575). HG is associated with dehydration and weight loss, which can result in hospitalisation and have significant detrimental effects for both mother and fetus. These include increased risk of morbidity, placental complications, small for gestational age birth, maternal psychological distress and increased risk of developmental delay for offspring (PMID: 35367190, PMID: 25898368, PMID: 23360164, PMID: 33713683, PMID: 21413857) .
A recent study (PMID: 38092039) made great progress in understanding a major cause of NVP and HG. Using a variety of analyses, especially of human genetic data, the authors showed that maternal sensitivity to a protein released from the placenta called growth differentiation factor 15 (GDF15), is key causal risk factor. This finding was exciting as it suggested avenues for future research into prevention or treatment. Evidence for the role of GDF15 included associations of variants (single letter changes in the DNA code) in the GDF15 gene region with both risk of NVP or HG, and with GDF15 levels in the blood (PMID: 35218128, PMID:29563502, PMID: 38092039). The finding that women who have naturally low levels of GDF15 are more sensitive to the GDF15 released from the placenta and more susceptible to NVP and HG, raised the possibility that a fetal genetic variants which increase GDF15 production may also influence HG or NVP risk. There was some evidence in a small sample that the genotype of the fetus, relative to the mother, may be associated with the proportion of fetal-placental derived GDF15 contributing to circulating GDF15, potentially mediating experiences of nausea and vomiting (PMID: 38092039). However, analyses of maternal and fetal genotype data in well powered samples are needed to confirm this, which is the focus of our proposed project. We aim to explore the maternal and fetal genetic contributions of genetic variants to nausea and vomiting during pregnancy.