Nausea and Vomiting of Pregnancy and HG Risk Genes Associated With Blood Levels, Sleep, Stomach Pain, and Other Traits [23N

Abstract

INTRODUCTION: Our genome-wide association study (GWAS) and replication study of nausea and vomiting of pregnancy (NVP) and Hyperemesis Gravidarum (HG) implicates the placenta and appetite hormone gene GDF15, its receptor GFRAL, PGR, and IGFBP7. The purpose of this study was to determine whether these genes and summary statistics overlap with other traits. METHODS: The GWAS catalog was searched for risk genes. The database and web interface platform, LD Hub, was used for genetic correlation analysis of summary statistics. RESULTS: Among 4220 GWASes, the HG risk locus GDF15 was associated with GDF15 protein levels, periodontitis, and lupus. GFRAL was associated with glomerular filtration rate, blood urea nitrogen levels, insomnia, body mass index, periodontal inflammation, blood protein levels, osteoporosis, and HIV-1 infection. IGFBP7 was associated with IGFBP7 protein levels, IgG glycosylation, diastolic blood pressure, brain volume in infants, heel bone mineral density, alcohol consumption, itch intensity from mosquitoes, and cotinine glucuronidation. PGR was associated with diastolic blood pressure, endometriosis/endometrial cancer, menstrual cycle length, lung adenocarcinoma, height, and adolescent idiopathic scoliosis. Among 855 pairs of traits, the leading findings showed variants increasing HG also increase stomach pain (P=.0004) and variants increasing NVP also increase sleeplessness/insomnia (P=1.37E-14). CONCLUSION: The finding that variants in GDF15 and IGFBP7 are associated with blood protein levels supports our study showing abnormal levels of GDF15 and IGFBP7 in women with HG. Overlap of the genes with other conditions provides biological insight. Associations with poor sleep and stomach pain may have implications for treatment strategies for NVP/HG.