Maternal and fetal genetic contribution to gestational weight gain

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  • dc.contributor.author Warrington, Nicole M.
  • dc.contributor.author Espinosa Díaz, Ana
  • dc.contributor.author Guxens Junyent, Mònica
  • dc.contributor.author Kogevinas, Manolis
  • dc.contributor.author Bustamante Pineda, Mariona
  • dc.contributor.author Lawlor, Deborah
  • dc.date.accessioned 2019-11-21T12:50:28Z
  • dc.date.available 2019-11-21T12:50:28Z
  • dc.date.issued 2018
  • dc.description.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 and methods: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 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 (for example, maternal body mass index (BMI) and glucose, birth weight). Results: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established 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 birth weight variants were largely unrelated to GWG. Conclusions: 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 diabetes with GWG.
  • dc.description.sponsorship The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement (grant number 669545; DevelopObese), the US National Institute of Health (R01 DK10324), Wellcome Trust (WT088806) and UK Medical Research Council (MC_UU_12013/4 and MC_UU_12013/5).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Warrington NM, Richmond R, Fenstra B, Myhre R, Gaillard R, Paternoster L et al. Maternal and fetal genetic contribution to gestational weight gain. Int J Obes (Lond). 2018; 42(4):775-784. DOI 10.1038/ijo.2017.248
  • dc.identifier.doi http://dx.doi.org/10.1038/ijo.2017.248
  • dc.identifier.issn 0307-0565
  • dc.identifier.uri http://hdl.handle.net/10230/42917
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Int J Obes (Lond). 2018; 42(4):775-784
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/669545
  • dc.rights © The Author(s) 2018. 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/
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Development
  • dc.subject.keyword Epidemiology
  • dc.subject.keyword Weight management
  • dc.title Maternal and fetal genetic contribution to gestational weight gain
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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