Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth
(2023) In Nature Genetics 55(11). p.1807-1819- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8987bd1e-b0f3-4e7b-9663-74ee79f05987
- author
- Beaumont, R.N. ; Fadista, J. LU ; Feenstra, B. and Njølstad, P.R.
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 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
- in
- Nature Genetics
- volume
- 55
- issue
- 11
- pages
- 13 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85173791824
- pmid:37798380
- ISSN
- 1061-4036
- DOI
- 10.1038/s41588-023-01520-w
- language
- English
- LU publication?
- yes
- id
- 8987bd1e-b0f3-4e7b-9663-74ee79f05987
- date added to LUP
- 2024-01-16 14:10:22
- date last changed
- 2024-04-02 20:30:17
@article{8987bd1e-b0f3-4e7b-9663-74ee79f05987,
abstract = {{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.}},
author = {{Beaumont, R.N. and Fadista, J. and Feenstra, B. and Njølstad, P.R.}},
issn = {{1061-4036}},
keywords = {{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}},
language = {{eng}},
number = {{11}},
pages = {{1807--1819}},
publisher = {{Nature Publishing Group}},
series = {{Nature Genetics}},
title = {{Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth}},
url = {{http://dx.doi.org/10.1038/s41588-023-01520-w}},
doi = {{10.1038/s41588-023-01520-w}},
volume = {{55}},
year = {{2023}},
}