2 research outputs found
Pregnancy-associated bleeding and genetics:Five sequence variants in the myometrium and progesterone signaling pathway are associated with postpartum hemorrhage
Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes, HAND2, TBX3, and RAP2C/FRMD7, at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR). Furthermore, there were strong genetic correlations with birth weight, gestational duration, and uterine fibroids. Early bleeding during pregnancy (28,898 cases and 302,894 controls) yielded no genome-wide association signals, but showed strong genetic correlation with a variety of human traits, indicative of polygenic and pleiotropic effects. Our results suggest that postpartum bleeding is related to myometrium dysregulation, whereas early bleeding is a complex trait related to underlying health and possibly socioeconomic status
Maternal and fetal genetic contribution to gestational weight gain
BACKGROUND: Clinical recommendations to limit gestational weight
gain (GWG) imply high GWG is causally related to adverse
outcomes in mother or offspring, but GWG is the sum of several
inter-related complex phenotypes (maternal fat deposition and
vascular expansion, placenta, amniotic fluid and fetal growth).
Understanding the genetic contribution to GWG could help clarify
the potential effect of its different components on maternal and
offspring health. Here we explore the genetic contribution to
total, early and late GWG. PARTICIPANTS AND METHODS: A
genome-wide association study was used to identify maternal and
fetal variants contributing to GWG in up to 10 543 mothers and
16 317 offspring of European origin, with replication in 10 660
mothers and 7561 offspring. Additional analyses determined the
proportion of variability in GWG from maternal and fetal common
genetic variants and the overlap of established genome-wide
significant variants for phenotypes relevant to GWG (e.g.
maternal BMI and glucose, birthweight). RESULTS: Approximately
20% of the variability in GWG was tagged by common maternal
genetic variants, and the fetal genome made a surprisingly minor
contribution to explaining variation in GWG. Variants near the
Pregnancy Specific Beta-1-Glycoprotein 5 (PSG5) gene reached
genome-wide significance (P=1.71 x 10-8) for total GWG in the
offspring genome, but did not replicate. Some established
variants associated with increased BMI, fasting glucose and type
2 diabetes were associated with lower early, and higher later
GWG. Maternal variants related to higher systolic blood pressure
were related to lower late GWG. Established maternal and fetal
birthweight variants were largely unrelated to GWG. CONCLUSION:
We found a modest contribution of maternal common variants to
GWG and some overlap of maternal BMI, glucose and type 2
diabetes variants with GWG. These findings suggest that
associations between GWG and later offspring/maternal outcomes
may be due to the relationship of maternal BMI and diabetes with
GWG.International Journal of Obesity accepted article preview
online, 09 October 2017. doi:10.1038/ijo.2017.248