In:
Obstetrics & Gynecology, Ovid Technologies (Wolters Kluwer Health), Vol. 141, No. 5S ( 2023-05), p. 73S-74S
Abstract:
Hyperemesis gravidarum (HG), a highly heritable condition, complicates ∼3% of pregnancies and is associated with adverse outcomes related to inadequate maternal weight gain. We report the largest-ever genome-wide association study (GWAS) of HG, composed of 8,960 cases and 369,843 controls. We identified associations with genes encoding GDF15 and its receptor GFRAL, so we compared changes in circulating GDF15 to weight gain in hospitalized HG patients. METHODS: We performed a meta-analysis of six independent studies: a multiancestry whole-exome sequencing study from the United States, four GWASs of European ancestry from 23andMe, Inc., research participants, FinnGen, Estonian and UK Biobanks, and a GWAS of British Bangladeshis and Pakistanis. We also studied three hospitalized HG patients, assessing serum GDF15 and weight at admission and discharge. Institutional review board approval was obtained. RESULTS: GDF15 was the greatest significant risk factor for HG in the meta-analysis ( P = 2.47E-47) and each individual GWAS. Association with GFRAL ( P =8.85E-09) further implicates the GDF15/GFRAL pathway in HG etiology. The solitary HG patient with lower GDF15 at discharge was the only one who gained weight during hospitalization. CONCLUSION: Overall, this study contributes to our understanding of the biology of HG and may inform future research evaluating new treatment avenues. Of note, drugs blocking GDF15/GFRAL mitigate appetite, weight loss, and vomiting in animal models. These drugs are currently in clinical trials of cancer cachexia, a disease with similar symptoms to HG. The strong link of HG to the GDF15/GFRAL pathway suggests that these drugs, if safe, hold great promise for improving symptoms and weight gain in HG patients.
Type of Medium:
Online Resource
ISSN:
0029-7844
DOI:
10.1097/01.AOG.0000930864.74571.0c
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2023
detail.hit.zdb_id:
2012791-1
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