e-Article
Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth
Document Type
Article
Author
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; Rivadeneira, Fernando; Sebert, Sylvain; Shields, Beverley M.; Stoltenberg, Camilla; Surakka, Ida; Thørner, Lise Wegner; Ullum, Henrik; Vaarasmaki, 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.
Source
Nature Genetics; November 2023, Vol. 55 Issue: 11 p1807-1819, 13p
Subject
Language
ISSN
10614036; 15461718
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.