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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Nature Genetics |
Vol/bind | 55 |
Udgave nummer | 11 |
Sider (fra-til) | 1807-1819 |
Antal sider | 13 |
ISSN | 1061-4036 |
DOI | |
Status | Udgivet - 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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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; 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.
I: Nature Genetics, Bind 55, Nr. 11, 2023, s. 1807-1819.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth
AU - Beaumont, Robin N.
AU - Flatley, Christopher
AU - Vaudel, Marc
AU - Wu, Xiaoping
AU - Chen, Jing
AU - Moen, Gunn Helen
AU - Skotte, Line
AU - Helgeland, Øyvind
AU - Solé-Navais, Pol
AU - Banasik, Karina
AU - Albiñana, Clara
AU - Ronkainen, Justiina
AU - Fadista, João
AU - Stinson, Sara Elizabeth
AU - Trajanoska, Katerina
AU - Wang, Carol A.
AU - Westergaard, David
AU - Srinivasan, Sundararajan
AU - Sánchez-Soriano, Carlos
AU - Bilbao, Jose Ramon
AU - Allard, Catherine
AU - Groleau, Marika
AU - Kuulasmaa, Teemu
AU - Leirer, Daniel J.
AU - White, Frédérique
AU - Jacques, Pierre Étienne
AU - Cheng, Haoxiang
AU - Hao, Ke
AU - Andreassen, Ole A.
AU - Åsvold, Bjørn Olav
AU - Atalay, Mustafa
AU - Bhatta, Laxmi
AU - Bouchard, Luigi
AU - Brumpton, Ben Michael
AU - Brunak, Søren
AU - Bybjerg-Grauholm, Jonas
AU - Ebbing, Cathrine
AU - Elliott, Paul
AU - Engelbrechtsen, Line
AU - Erikstrup, Christian
AU - Estarlich, Marisa
AU - Franks, Stephen
AU - Gaillard, Romy
AU - Geller, Frank
AU - Grove, Jakob
AU - Hougaard, David M.
AU - Kajantie, Eero
AU - Morgen, Camilla S.
AU - Nohr, Ellen A.
AU - Nyegaard, Mette
AU - Palmer, Colin N.A.
AU - Pedersen, Ole Birger
AU - Rivadeneira, Fernando
AU - Sebert, Sylvain
AU - Shields, Beverley M.
AU - Stoltenberg, Camilla
AU - Surakka, Ida
AU - Thørner, Lise Wegner
AU - Ullum, Henrik
AU - Vaarasmaki, Marja
AU - Vilhjalmsson, Bjarni J.
AU - Willer, Cristen J.
AU - Lakka, Timo A.
AU - Gybel-Brask, Dorte
AU - Bustamante, Mariona
AU - Hansen, Torben
AU - Pearson, Ewan R.
AU - Reynolds, Rebecca M.
AU - Ostrowski, Sisse R.
AU - Pennell, Craig E.
AU - Jaddoe, Vincent W.V.
AU - Felix, Janine F.
AU - Hattersley, Andrew T.
AU - Melbye, Mads
AU - Lawlor, Deborah A.
AU - Hveem, Kristian
AU - Werge, Thomas
AU - Nielsen, Henriette Svarre
AU - Magnus, Per
AU - Evans, David M.
AU - Jacobsson, Bo
AU - Järvelin, Marjo Riitta
AU - Zhang, Ge
AU - Hivert, Marie France
AU - Johansson, Stefan
AU - Freathy, Rachel M.
AU - Feenstra, Bjarke
AU - Njølstad, Pål R.
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41588-023-01520-w
DO - 10.1038/s41588-023-01520-w
M3 - Journal article
C2 - 37798380
AN - SCOPUS:85173791824
VL - 55
SP - 1807
EP - 1819
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -