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Maternal and fetal genetic contribution to gestational weight gain

Maternal and fetal genetic contribution to gestational weight gain
Maternal and fetal genetic contribution to gestational weight gain
Background: clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. Participants andMethods: a genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10,543 mothers and up to 16,317 offspring of European origin, with replication in 10,660 mothers and 7,561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (e.g. maternal BMI and glucose, birthweight).Results: we found that approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and that the fetal genome made a surprisingly minor contribution to explaining variation in GWG. We were unable to identify any genetic variants that reached genome-wide levels of significance (P<5x10-8) and replicated. Some established maternal variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birthweight variants were largely unrelated to GWG.Conclusion: we found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and gestational diabetes with GWG.
0307-0565
775-784
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Warrington, Nicole M., Richmond, Rebecca, Feenstra, Bjarke, Myhre, Ronny, Gaillard, Romy, Paternoster, Lavinia, Wang, Carol A., Beaumont, Robin N, Das, Shikta, Murcia, Mario, Barton, Sheila, Espinosa, Ana, Thiering, Elisabeth, Atalay, Mustafa, Pitkänen, Niina, Ntalla, Ioanna, Jonsson, Anna E, Freathy, Rachel M., Karhunen, Ville, Tiesler, Carla M.T., Allard, Catherine, Crawford, Andrew, Ring, Susan M., Melbye, Mads, Magnus, Per, Rivadeneira, Fernando, Skotte, Line, Hansen, Torben, Marsh, Julie, Guxens, Mònica, Holloway, John, Grallert, Harald, Jaddoe, Vincent W.V., Lowe, William L, Roumeliotaki, Theano, Hattersley, Andrew T., Lindi, Virpi, Pahkala, Katja, Panoutsopoulou, Kalliope, Standl, Marie, Flexeder, Claudia, Bouchard, Luigi, Nohr, Ellen Aagaard, Marina, Loreto Santa, Kogevinas, Manolis, Niinikoski, Harri, Dedoussis, George, Heinrich, Joachim, Reynolds, Rebecca M., Lakka, Timo A., Zeggini, Eleftheria, Raitakari, Olli T., Chatzi, Leda, Inskip, Hazel, Bustamante, Mariona, Hivert, Marie-France, Jarvelin, Marjo-Riitta, Sørensen, Thorkild I.A., Pennell, Craig, Felix, Janine F., Jacobsson, Bo, Geller, Frank, Evans, David M. and Lawlor, Debbie A. (2018) Maternal and fetal genetic contribution to gestational weight gain. International Journal of Obesity, 42 (4), 775-784. (doi:10.1038/ijo.2017.248).

Record type: Article

Abstract

Background: clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. Participants andMethods: a genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10,543 mothers and up to 16,317 offspring of European origin, with replication in 10,660 mothers and 7,561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (e.g. maternal BMI and glucose, birthweight).Results: we found that approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and that the fetal genome made a surprisingly minor contribution to explaining variation in GWG. We were unable to identify any genetic variants that reached genome-wide levels of significance (P<5x10-8) and replicated. Some established maternal variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birthweight variants were largely unrelated to GWG.Conclusion: we found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and gestational diabetes with GWG.

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Accepted/In Press date: 4 September 2017
e-pub ahead of print date: 9 October 2017
Published date: 1 April 2018

Identifiers

Local EPrints ID: 414453
URI: https://eprints.soton.ac.uk/id/eprint/414453
ISSN: 0307-0565
PURE UUID: c613cd19-0431-467d-88e5-bfce6597fe82
ORCID for Sheila Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Hazel Inskip: ORCID iD orcid.org/0000-0001-8897-1749

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Date deposited: 29 Sep 2017 16:31
Last modified: 03 Dec 2019 05:50

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Contributors

Author: Nicole M. Warrington
Author: Rebecca Richmond
Author: Bjarke Feenstra
Author: Ronny Myhre
Author: Romy Gaillard
Author: Lavinia Paternoster
Author: Carol A. Wang
Author: Robin N Beaumont
Author: Shikta Das
Author: Mario Murcia
Author: Sheila Barton ORCID iD
Author: Ana Espinosa
Author: Elisabeth Thiering
Author: Mustafa Atalay
Author: Niina Pitkänen
Author: Ioanna Ntalla
Author: Anna E Jonsson
Author: Rachel M. Freathy
Author: Ville Karhunen
Author: Carla M.T. Tiesler
Author: Catherine Allard
Author: Andrew Crawford
Author: Susan M. Ring
Author: Mads Melbye
Author: Per Magnus
Author: Fernando Rivadeneira
Author: Line Skotte
Author: Torben Hansen
Author: Julie Marsh
Author: Mònica Guxens
Author: John Holloway ORCID iD
Author: Harald Grallert
Author: Vincent W.V. Jaddoe
Author: William L Lowe
Author: Theano Roumeliotaki
Author: Andrew T. Hattersley
Author: Virpi Lindi
Author: Katja Pahkala
Author: Kalliope Panoutsopoulou
Author: Marie Standl
Author: Claudia Flexeder
Author: Luigi Bouchard
Author: Ellen Aagaard Nohr
Author: Loreto Santa Marina
Author: Manolis Kogevinas
Author: Harri Niinikoski
Author: George Dedoussis
Author: Joachim Heinrich
Author: Rebecca M. Reynolds
Author: Timo A. Lakka
Author: Eleftheria Zeggini
Author: Olli T. Raitakari
Author: Leda Chatzi
Author: Hazel Inskip ORCID iD
Author: Mariona Bustamante
Author: Marie-France Hivert
Author: Marjo-Riitta Jarvelin
Author: Thorkild I.A. Sørensen
Author: Craig Pennell
Author: Janine F. Felix
Author: Bo Jacobsson
Author: Frank Geller
Author: David M. Evans
Author: Debbie A. Lawlor

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