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Nat Commun. 2018 Mar 21;9(1):1178. doi: 10.1038/s41467-018-03258-0.

Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum.

Author information

1
Division of Hematology-Oncology, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA. mfejzo@mednet.ucla.edu.
2
Department of Maternal-Fetal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. mfejzo@mednet.ucla.edu.
3
23andMe, Inc., Mountain View, CA, 94041, USA.
4
Amgen Inc., South San Francisco, CA, 94080, USA.
5
Hyperemesis Education and Research Foundation, Damascus, OR, 97089, USA.
6
Department of Statistics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
7
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
8
Division of Hematology-Oncology, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
9
Department of Maternal-Fetal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.

Abstract

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3-2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10-8) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.

PMID:
29563502
PMCID:
PMC5862842
DOI:
10.1038/s41467-018-03258-0
[Indexed for MEDLINE]
Free PMC Article

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