Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth
Beaumont, Robin N.; Flatley, Christopher; Vaudel, Marc; Wu, Xiaoping; Chen, Jing; Moen, Gunn-Helen; Skotte, Line; Helgeland, Øyvind; Solé-Navais, Pol; Banasik, Karina; Albiñana, Clara; Ronkainen, Justiina; Fadista, João; Stinson, Sara Elizabeth; Trajanoska, Katerina; Wang, Carol A.; Westergaard, David; Srinivasan, Sundararajan; Sánchez-Soriano, Carlos; Bilbao, Jose Ramon; Allard, Catherine; Groleau, Marika; Kuulasmaa, Teemu; Leirer, Daniel J.; White, Frédérique; Jacques, Pierre-Étienne; Cheng, Haoxiang; Hao, Ke; Andreassen, Ole A.; Åsvold, Bjørn Olav; Atalay, Mustafa; Bhatta, Laxmi; Bouchard, Luigi; Brumpton, Ben Michael; Brunak, Søren; Bybjerg-Grauholm, Jonas; Ebbing, Cathrine; Elliott, Paul; Engelbrechtsen, Line; Erikstrup, Christian; Estarlich, Marisa; Franks, Stephen; Gaillard, Romy; Geller, Frank; Grove, Jakob; Hougaard, David M.; Kajantie, Eero; Morgen, Camilla S.; Nohr, Ellen A.; Nyegaard, Mette; Palmer, Colin N. A.; Pedersen, Ole Birger; The Early Growth Genetics (EGG) Consortium; Rivadeneira, Fernando; Sebert, Sylvain; Shields, Beverley M.; Stoltenberg, Camilla; Surakka, Ida; Thørner, Lise Wegner; Ullum, Henrik; Vääräsmäki, Marja; Vilhjalmsson, Bjarni J.; Willer, Cristen J.; Lakka, Timo A.; Gybel-Brask, Dorte; Bustamante, Mariona; Hansen, Torben; Pearson, Ewan R.; Reynolds, Rebecca M.; Ostrowski, Sisse R.; Pennell, Craig E.; Jaddoe, Vincent W. V.; Felix, Janine F.; Hattersley, Andrew T.; Melbye, Mads; Lawlor, Deborah A.; Hveem, Kristian; Werge, Thomas; Nielsen, Henriette Svarre; Magnus, Per; Evans, David M.; Jacobsson, Bo; Järvelin, Marjo-Riitta; Zhang, Ge; Hivert, Marie-France; Johansson, Stefan; Freathy, Rachel M.; Feenstra, Bjarke; Njølstad, Pål R. (2023-10-05)
Springer
05.10.2023
Beaumont, R.N., Flatley, C., Vaudel, M. et al. Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth. Nat Genet 55, 1807–1819 (2023). https://doi.org/10.1038/s41588-023-01520-w.
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© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202312153829
https://urn.fi/URN:NBN:fi:oulu-202312153829
Tiivistelmä
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.
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.
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