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

Early Growth Genetics (EGG) Consortium, Robin N Beaumont, Christopher Flatley, Marc Vaudel, Xiaoping Wu, Jing Chen, Gunn-Helen Moen, Line Skotte, Øyvind Helgeland, Pol Solé-Navais, Karina Banasik, Clara Albiñana, Justiina Ronkainen, João Fadista, Sara Elizabeth Stinson, Katerina Trajanoska, Carol A Wang, David Westergaard, Sundararajan Srinivasan, Carlos Sanchez-SorianoJose Ramon Bilbao, Catherine Allard, Marika Groleau, Teemu Kuulasmaa, Daniel J Leirer, Frédérique White, Pierre-Étienne Jacques, Haoxiang Cheng, Ke Hao, Ole A Andreassen, Bjørn Olav Åsvold, Mustafa Atalay, Laxmi Bhatta, Luigi Bouchard, Ben Michael Brumpton, Søren Brunak, Jonas Bybjerg-Grauholm, Cathrine Ebbing, Paul Elliott, Line Engelbrechtsen, Christian Erikstrup, Marisa Estarlich, Stephen Franks, Romy Gaillard, Frank Geller, Jakob Grove, David M Hougaard, Eero Kajantie, Camilla S Morgen, Ole Birger Pedersen, Dorte Gybel-Brask, Stefan Johansson*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

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.

OriginalsprogEngelsk
Sider (fra-til)1807-1819
Antal sider13
TidsskriftNature Genetics
Vol/bind55
Udgave nummer11
Tidlig onlinedato5 okt. 2023
DOI
StatusUdgivet - nov. 2023

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© 2023. The Author(s).

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