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Get Free AccessAbstract A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight after term delivery 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 confidently classified as fetal only, four maternal only, 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 twelve 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 risk of preeclampsia or shorter gestational duration. Moreover, these analyses support a role for insulin produced by the fetus in regulating the growth of the placenta, providing a key link between fetal and placental growth.
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 Stinson, Katerina Trajanoska, Carol A. Wang, David Westergaard, Sundararajan Srinivasan, Carlos Sánchez-Soriano, José Ramón 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 Brumpton, Søren Brunak, Jonas Bybjerg‐Grauholm, Cathrine Ebbing, Paul Elliott, Line Engelbrechtsen, Christian Erikstrup, Marisa Estarlich, Steve Franks, Romy Gaillard, Frank Geller, Jakob Grove, David M. Hougaard, Eero Kajantie, Camilla S. Morgen, Ellen A. Nøhr, Mette Nyegaard, Nicholette D. Palmer, Ole Birger Pedersen, Fernando Rivadeneira, Sylvain Sebért, Beverley M. Shields, Camilla Stoltenberg, Ida Surakka, Lise Wegner Thørner, Henrik Ullum, Marja Vääräsmäki, Bjarni J. Vilhjálmsson, Cristen J. Willer, Timo A. Lakka, Dorte Jensen Gybel-Brask, Mariona Bustamante, Torben Hansen, Ewan R. Pearson, Rebecca M. Reynolds, Sisse Rye Ostrowski, Craig E. Pennell, Vincent W. V. Jaddoe, Janine F. Felix, Andrew T. Hattersley, Mads Melbye, Debbie A. Lawlor, Kristian Hveem, Thomas Werge, Henriette Svarre Nielsen, Per Magnus, David M. Evans, Bo Jacobsson, Paul M Ridker, Ge Zhang, Marie‐France Hivert, Stefan Johansson, Rachel M. Freathy, Bjarke Feenstra, Pål R. Njølstad (2022). Genome-wide association study of placental weight in 179,025 children and parents reveals distinct and shared genetic influences between placental and fetal growth. , DOI: https://doi.org/10.1101/2022.11.25.22282723.
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Type
Preprint
Year
2022
Authors
88
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1101/2022.11.25.22282723
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