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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Appetite / genetics
  • Chromosomes, Human, Pair 19
  • Chromosomes, Human, Pair 4
  • Cohort Studies
  • Female
  • Gene Expression
  • Genome, Human
  • Genome-Wide Association Study
  • Growth Differentiation Factor 15 / genetics*
  • Growth Differentiation Factor 15 / metabolism
  • Humans
  • Hyperemesis Gravidarum / genetics*
  • Hyperemesis Gravidarum / metabolism
  • Hyperemesis Gravidarum / physiopathology
  • Insulin-Like Growth Factor Binding Proteins / genetics*
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Nausea / etiology
  • Nausea / genetics*
  • Nausea / metabolism
  • Nausea / physiopathology
  • Phenotype
  • Placenta / metabolism*
  • Placenta / pathology
  • Pregnancy
  • Pregnancy Complications / genetics*
  • Pregnancy Complications / metabolism
  • Pregnancy Complications / physiopathology
  • Quantitative Trait Loci
  • Risk Factors
  • Severity of Illness Index
  • Vomiting / genetics*
  • Vomiting / metabolism
  • Vomiting / physiopathology

Substances

  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Insulin-Like Growth Factor Binding Proteins
  • insulin-like growth factor binding protein-related protein 1