Lastly, we shed light on the expression of risk loci during maternal and fetal placental development, their effects on nausea and vomiting across gestation, and their maternal and fetal/paternal contributions to risk.

We find effect-sizes are largely consistent across studies/ancestries, providing evidence of shared genetic architecture.

We also validate the 4 loci identified in our previous studies and reaffirm variants in GDF15 are the greatest genetic risk factor for HG, supporting upcoming clinical trial(s) largely based on this finding.

Notably, 6 of the 10 loci (GDF15, GFRAL, TCF7L2, IGSF11, FSHB, IGFBP7) may be associated with insulin and altered glucose metabolism, providing novel insight into the pathobiology of nausea and vomiting of pregnancy.

We identify 6 novel risk loci that provide new pathways to explore etiological mechanisms and novel therapeutic avenues. In particular TCF7L2, is a gene that encodes a key risk factor for type 2 diabetes (and gestational diabetes) and may control expression of GLP-1.