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

Robin N. Beaumont, Christopher Flatley, Marc Vaudel, Xiaoping Wu, Jing Chen, Gunn-Helen Moen, Line Skotte, Øyvind Helgeland, Pol Sole-Navis, Karina Banasik, Justiina Ronkainen, Clara Albinana, Justiina Ronkainen, Joao 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, Frederique White, Pierre-Etienne Jacques, Haixiang Cheng, He Hao, Ole A Andreassen, Bjorn Olav Asvold, Mustafa Atalay, Laxmi Bhatta, Luigi Bouchard, Ben Michael Brumpton, Soren Brunak, Jonas Bybjerg-Grauholm, Catherine Ebbing, Paul Elliott, Line Engelbrechtsen, Christian Erikstrup, Marissa Estarlich, Stephen Franks, Romy Gaillard, Frank Geller, Jacob Grove, David M. Hougaard, Eero Kajantie, Camilla S Morgen, Ellen Aagaard Nohr, Mette Nyegaard, Colin N. A. Palmer, Ole Birger Pedersen, , Fernando Rivadeneira, Sylvain Sebert, Beverley M. Shields, Camilla Stoltenberg, Ida Surakka, Lise Wegner Thorner, Henrik Ullum, Marja Vaarassmaki, Bjarni J Vilhjalmsson, Cristen J Willer, Timo A Lakka, Dorte Gybel-Brask, Mariona Bustamante, Torben Hansen, Ewan R. Pearson, Rebecca M Reynolds, Sissi R Ostrowski, Craig E. Pennell, Vincent W. V. Jaddoe, Janine F Felix, Andrew T. Hattersley, Mads Melbye, Deborah A. Lawlor, Kristian Hveem, Thomas Werge, Henriette Svarre Nielsen, Per Magnus, David M. Evans, Bo Jacobsson, Marjo-Riitta Jarvelin, Ge Zhang, Marie-France Hivert, Stefan Johansson (Lead / Corresponding author), Rachel M. Freathy (Lead / Corresponding author), Bjarke Feenstra (Lead / Corresponding author), Pal R. Njolstad (Lead / Corresponding author)

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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.
Original languageEnglish
Pages (from-to)1807-1819
Number of pages13
JournalNature Genetics
Volume55
Issue number11
Early online date5 Oct 2023
DOIs
Publication statusPublished - Nov 2023

Keywords

  • Genetic association study
  • Genetics research

ASJC Scopus subject areas

  • Genetics

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