23andMe Backed Study Reveals Genetic Risk Factors For Hyperemesis Gravidarum

Figure of genome-wide association scans for nausea and vomiting of pregnancy. The Manhattan plot shows distribution of association test statistics vs. genomic position for SCAN1 (binary phenotype). Source Figure 1a of Fejzo MS, et al.'s paper [2]. No changes made. Creative Commons Attribution 4.0 International (CC BY 4.0).
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Nausea and vomiting vary considerably in duration and severity in pregnancy but are common complaints [1]. Hyperemesis gravidarum (HG) is a condition that occurs in 0.3–2% of pregnancies and is associated with maternal and fetal morbidity, which represents the extreme end of the spectrum associated with dehydration and weight loss. Sometimes hospitalization is required due to the severity of the symptoms. It was not known whether there were any genetic underpinnings until now with a new study published in Nature Communications [2].

Customers of 23andMe that provide a saliva sample to the company, are participating in a kind of commercial biobank [3]. They consent to having 23andMe and its contractors access and analyze their stored sample, using genetic sequencing or other technologies. Unless 23andMe notify otherwise, the company will store the customers sample for a minimum of one year and a maximum of ten years, at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.

A study by researchers at the University of California at Los Angeles (UCLA) in collaboration with 23andMe carried out a genome-wide association study (GWAS) of approximately 52,000 of the companies consenting female customers. The GWAS implicated genes at two genomic loci called GDF15 and IGFBP7 respectively, both of which are known to be involved in placentation, appetite, and cachexia, a disease with similar symptoms to HG, for example debilitating fatigue, weight loss and muscle wasting. It causes death in about 20% of cancer patients [4].

“It has long been assumed that the pregnancy hormones, human chorionic gonadotropin or estrogen, were the likely culprits of extreme nausea and vomiting, but our study found no evidence to support this,” stated lead author Marlena Fejzo [5].

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The GDF15 and IGFBP7 genes are turned on in the placenta during early pregnancy and code for proteins that regulate appetite. Dr. Fejzo said that “prior research has shown GDF15 is a regulator of physiological body weight and appetite via activation of neurons in the hypothalamus and area postrema (vomiting center) of the brain.”

Revealing the genetic risk factors for HG may in the future lead to treatments or improved pregnancy management.

 

Sources

  1. Management of hyperemesis gravidarum. Drug Ther Bull. 2013;51(11):126-9. doi: 10.1136/dtb.2013.11.0215. Review. PubMed PMID: 24227770
  2. Fejzo MS, et al. Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Nat Commun. 2018;9(1):1178. doi: 10.1038/s41467-018-03258-0. PubMed PMID: 29563502
  3. https://www.23andme.com/about/biobanking/
  4. Fox KM, et al. Estimation of Cachexia among Cancer Patients Based on Four Definitions. J Oncol. 2009;2009:693458. doi:10.1155/2009/693458. PubMed PMID: 19587829
  5. http://newsroom.ucla.edu/releases/two-genes-likely-play-key-role-in-extreme-nausea-and-vomiting-during-pregnancy