Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.

• A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)

Keyword

amino acid

antibody

potassium channel KCNQ1

adult

amino acid transport

Article

birth weight

controlled study

female

fetus

fetus growth

gene locus

genetic correlation

genome

genome-wide association study

genotype

gestational age

human

major clinical study

male

Mendelian randomization analysis

morphology

placenta

placenta development

placenta weight

preeclampsia

pregnancy

pregnancy complication

progeny

Publication and Content Type

ref (subject category)

art (subject category)