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

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  • Robin N. Beaumont
  • Christopher Flatley
  • Marc Vaudel
  • Xiaoping Wu
  • Jing Chen
  • Gunn Helen Moen
  • Line Skotte
  • Øyvind Helgeland
  • Pol Solé-Navais
  • Clara Albiñana
  • Justiina Ronkainen
  • João Fadista
  • Katerina Trajanoska
  • Carol A. Wang
  • Sundararajan Srinivasan
  • Carlos Sánchez-Soriano
  • Jose 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
  • Jonas Bybjerg-Grauholm
  • Cathrine Ebbing
  • Paul Elliott
  • Christian Erikstrup
  • Marisa Estarlich
  • Stephen Franks
  • Romy Gaillard
  • Frank Geller
  • Jakob Grove
  • David M. Hougaard
  • Eero Kajantie
  • Camilla S. Morgen
  • Ellen A. Nohr
  • Colin N.A. Palmer
  • Fernando Rivadeneira
  • Sylvain Sebert
  • Beverley M. Shields
  • Camilla Stoltenberg
  • Ida Surakka
  • Lise Wegner Thørner
  • Henrik Ullum
  • Marja Vaarasmaki
  • Bjarni J. Vilhjalmsson
  • Cristen J. Willer
  • Timo A. Lakka
  • Dorte Gybel-Brask
  • Mariona Bustamante
  • Ewan R. Pearson
  • Rebecca M. Reynolds
  • Craig E. Pennell
  • Vincent W.V. Jaddoe
  • Janine F. Felix
  • Andrew T. Hattersley
  • Deborah A. Lawlor
  • Kristian Hveem
  • Per Magnus
  • David M. Evans
  • Bo Jacobsson
  • Marjo Riitta Järvelin
  • Ge Zhang
  • Marie France Hivert
  • Stefan Johansson
  • Rachel M. Freathy
  • Bjarke Feenstra
  • Pål R. Njølstad

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
TidsskriftNature Genetics
Vol/bind55
Udgave nummer11
Sider (fra-til)1807-1819
Antal sider13
ISSN1061-4036
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We are grateful to M. Efremova and S.A. Teichmann (Wellcome Sanger Institute, Cambridge, UK) who shared the maternal–fetal interface single-cell RNA data. Full acknowledgements and details of supporting grants are found in the Supplementary Information.

Publisher Copyright:
© 2023, The Author(s).

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