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 Solé-Navais; Karina Banasik; Clara Albiñana; Justiina Ronkainen; João Fadista; Sara Elizabeth Stinson; Katerina Trajanoska; Carol A. Wang; David Westergaard; Sundararajan Srinivasan; Carlos Sánchez-Soriano; Jose Ramon 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 Michael Brumpton; Søren Brunak; Jonas Bybjerg-Grauholm; Cathrine Ebbing; Paul Elliott; Line Engelbrechtsen; Christian Erikstrup; Marisa Estarlich; Stephen Franks; Romy Gaillard; Frank Geller; Jakob Grove; David Hougaard; Eero Kajantie; Camilla S Morgen; Ellen A. Nohr; Mette Nyegaard; Colin N.A.  Palmer; Ole Birger Pedersen; The Early Growth Genetics (EGG) Consortium; Fernando Rivadeneira; Sylvain P Sebert; Beverley Shields; Camilla Stoltenberg; Ida Surakka; Lise Wegner Thørner; Henrik Ullum; Marja  Vaarasmaki; Bjarni J. Vilhjalmsson; Cristen J Willer; Timo A Lakka; Dorte  Gybel-Brask; Mariona Bustamante; Torben Hansen; Ewan R. Pearson; Rebecca Reynolds; Sisse Rye 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  Evans; Bo Jacobsson; Marjo-Riitta Järvelin; Ge Zhang; Marie-France Hivert; Stefan E. Johansson; Rachel M Freathy; Bjarke Feenstra; Pål Rasmus Njølstad

doi:10.1038/s41588-023-01520-w

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 Solé-Navais, Karina Banasik, Clara Albiñana, Justiina Ronkainen, João Fadista, Sara Elizabeth Stinson, Katerina Trajanoska, Carol A. Wang, David Westergaard, Sundararajan Srinivasan, Carlos Sánchez-Soriano, Jose Ramon BilbaoCatherine 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 Michael Brumpton, Søren Brunak, Jonas Bybjerg-Grauholm, Cathrine Ebbing, Paul Elliott, Line Engelbrechtsen, Christian Erikstrup, Marisa Estarlich, Stephen Franks, Romy Gaillard, Frank Geller, Jakob Grove, David Hougaard, Eero Kajantie, Camilla S Morgen, Ellen A. Nohr, Mette Nyegaard, Colin N.A. Palmer, Ole Birger Pedersen, The Early Growth Genetics (EGG) Consortium, Fernando Rivadeneira, Sylvain P Sebert, Beverley Shields, Camilla Stoltenberg, Ida Surakka, Lise Wegner Thørner, Henrik Ullum, Marja Vaarasmaki, Bjarni J. Vilhjalmsson, Cristen J Willer, Timo A Lakka, Dorte Gybel-Brask, Mariona Bustamante, Torben Hansen, Ewan R. Pearson, Rebecca Reynolds, Sisse Rye 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 Evans, Bo Jacobsson, Marjo-Riitta Järvelin, Ge Zhang, Marie-France Hivert, Stefan E. Johansson, Rachel M Freathy, Bjarke Feenstra, Pål Rasmus Njølstad

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

28 Downloads (Pure)

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 language	English
Journal	Nature Genetics
Volume	55
Issue	11
Pages (from-to)	1807-1819
Number of pages	13
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-023-01520-w
Publication status	Published - Nov 2023

Keywords

Birth Weight/genetics
Female
Fetal Development/genetics
Genome-Wide Association Study
Humans
Insulin
Male
Placenta/metabolism
Pregnancy

Access to Document

10.1038/s41588-023-01520-wLicence: CC BY

s41588-023-01520-wFinal published version, 12.8 MBLicence: CC BY

Cite this

Beaumont, R. N., Flatley, C., Vaudel, M., Wu, X., Chen, J., Moen, G. H., Skotte, L., Helgeland, Ø., Solé-Navais, P., Banasik, K., Albiñana, C., Ronkainen, J., Fadista, J., Stinson, S. E., Trajanoska, K., Wang, C. A., Westergaard, D., Srinivasan, S., Sánchez-Soriano, C., ... Njølstad, P. R. (2023). Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth. Nature Genetics, 55(11), 1807-1819. https://doi.org/10.1038/s41588-023-01520-w

@article{29f049c8bbaa4089806d66fa74a1cc94,

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

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.",

keywords = "Birth Weight/genetics, Female, Fetal Development/genetics, Genome-Wide Association Study, Humans, Insulin, Male, Placenta/metabolism, Pregnancy",

author = "Beaumont, {Robin N.} and Christopher Flatley and Marc Vaudel and Xiaoping Wu and Jing Chen and Moen, {Gunn Helen} and Line Skotte and {\O}yvind Helgeland and Pol Sol{\'e}-Navais and Karina Banasik and Clara Albi{\~n}ana and Justiina Ronkainen and Jo{\~a}o Fadista and Stinson, {Sara Elizabeth} and Katerina Trajanoska and Wang, {Carol A.} and David Westergaard and Sundararajan Srinivasan and Carlos S{\'a}nchez-Soriano and Bilbao, {Jose Ramon} and Catherine Allard and Marika Groleau and Teemu Kuulasmaa and Leirer, {Daniel J.} and Fr{\'e}d{\'e}rique White and Jacques, {Pierre {\'E}tienne} and Haoxiang Cheng and Ke Hao and Andreassen, {Ole A.} and {\AA}svold, {Bj{\o}rn Olav} and Mustafa Atalay and Laxmi Bhatta and Luigi Bouchard and Brumpton, {Ben Michael} and S{\o}ren Brunak and Jonas Bybjerg-Grauholm and Cathrine Ebbing and Paul Elliott and Line Engelbrechtsen and Christian Erikstrup and Marisa Estarlich and Stephen Franks and Romy Gaillard and Frank Geller and Jakob Grove and David Hougaard and Eero Kajantie and Morgen, {Camilla S} and Nohr, {Ellen A.} and Mette Nyegaard and Palmer, {Colin N.A.} and Pedersen, {Ole Birger} and {The Early Growth Genetics (EGG) Consortium} and Fernando Rivadeneira and Sebert, {Sylvain P} and Beverley Shields and Camilla Stoltenberg and Ida Surakka and Th{\o}rner, {Lise Wegner} and Henrik Ullum and Marja Vaarasmaki and Vilhjalmsson, {Bjarni J.} and Willer, {Cristen J} and Lakka, {Timo A} and Dorte Gybel-Brask and Mariona Bustamante and Torben Hansen and Pearson, {Ewan R.} and Rebecca Reynolds and Ostrowski, {Sisse Rye} and Pennell, {Craig E} and Jaddoe, {Vincent W V} and {F. Felix}, Janine and Hattersley, {Andrew T.} and Mads Melbye and Lawlor, {Deborah A.} and Kristian Hveem and Thomas Werge and Nielsen, {Henriette Svarre} and Per Magnus and David Evans and Bo Jacobsson and Marjo-Riitta J{\"a}rvelin and Ge Zhang and Marie-France Hivert and Johansson, {Stefan E.} and Freathy, {Rachel M} and Bjarke Feenstra and Nj{\o}lstad, {P{\aa}l Rasmus}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = nov,

doi = "10.1038/s41588-023-01520-w",

language = "English",

volume = "55",

pages = "1807--1819",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

}

Beaumont, RN, Flatley, C, Vaudel, M, Wu, X, Chen, J, Moen, GH, Skotte, L, Helgeland, Ø, Solé-Navais, P, Banasik, K, Albiñana, C, Ronkainen, J, Fadista, J, Stinson, SE, Trajanoska, K, Wang, CA, Westergaard, D, Srinivasan, S, Sánchez-Soriano, C, Bilbao, JR, Allard, C, Groleau, M, Kuulasmaa, T, Leirer, DJ, White, F, Jacques, PÉ, Cheng, H, Hao, K, Andreassen, OA, Åsvold, BO, Atalay, M, Bhatta, L, Bouchard, L, Brumpton, BM, Brunak, S, Bybjerg-Grauholm, J, Ebbing, C, Elliott, P, Engelbrechtsen, L, Erikstrup, C, Estarlich, M, Franks, S, Gaillard, R, Geller, F, Grove, J, Hougaard, D, Kajantie, E, Morgen, CS, Nohr, EA, Nyegaard, M, Palmer, CNA, Pedersen, OB, The Early Growth Genetics (EGG) Consortium, Rivadeneira, F, Sebert, SP, Shields, B, Stoltenberg, C, Surakka, I, Thørner, LW, Ullum, H, Vaarasmaki, M, Vilhjalmsson, BJ, Willer, CJ, Lakka, TA, Gybel-Brask, D, Bustamante, M, Hansen, T, Pearson, ER, Reynolds, R, Ostrowski, SR, Pennell, CE, Jaddoe, VWV, F. Felix, J, Hattersley, AT, Melbye, M, Lawlor, DA, Hveem, K, Werge, T, Nielsen, HS, Magnus, P, Evans, D, Jacobsson, B, Järvelin, M-R, Zhang, G, Hivert, M-F, Johansson, SE, Freathy, RM, Feenstra, B & Njølstad, PR 2023, 'Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth', Nature Genetics, vol. 55, no. 11, pp. 1807-1819. https://doi.org/10.1038/s41588-023-01520-w

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 et al.
In: Nature Genetics, Vol. 55, No. 11, 11.2023, p. 1807-1819.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › 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

AU - Kajantie, Eero

AU - Morgen, Camilla S

AU - Nohr, Ellen A.

AU - Nyegaard, Mette

AU - Palmer, Colin N.A.

AU - Pedersen, Ole Birger

AU - The Early Growth Genetics (EGG) Consortium

AU - Rivadeneira, Fernando

AU - Sebert, Sylvain P

AU - Shields, Beverley

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

AU - Ostrowski, Sisse Rye

AU - Pennell, Craig E

AU - Jaddoe, Vincent W V

AU - F. Felix, Janine

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

AU - Jacobsson, Bo

AU - Järvelin, Marjo-Riitta

AU - Zhang, Ge

AU - Hivert, Marie-France

AU - Johansson, Stefan E.

AU - Freathy, Rachel M

AU - Feenstra, Bjarke

AU - Njølstad, Pål Rasmus

PY - 2023/11

Y1 - 2023/11

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.

KW - Birth Weight/genetics

KW - Female

KW - Fetal Development/genetics

KW - Genome-Wide Association Study

KW - Humans

KW - Insulin

KW - Male

KW - Placenta/metabolism

KW - Pregnancy

UR - http://www.scopus.com/inward/record.url?scp=85173791824&partnerID=8YFLogxK

U2 - 10.1038/s41588-023-01520-w

DO - 10.1038/s41588-023-01520-w

M3 - Journal article

C2 - 37798380

AN - SCOPUS:85173791824

SN - 1061-4036

VL - 55

SP - 1807

EP - 1819

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this