University of Oulu

Warrington, N., Richmond, R., Fenstra, B., Myhre, R., Gaillard, R., Paternoster, L., Wang, C., Beaumont, R., Das, S., Murcia, M., Barton, S., Espinosa, A., Thiering, E., Atalay, M., Pitkänen, N., Ntalla, I., Jonsson, A., Freathy, R., Karhunen, V., Tiesler, C., Allard, C., Crawford, A., Ring, S., Melbye, M., Magnus, P., Rivadeneira, F., Skotte, L., Hansen, T., Marsh, J., Guxens, M., Holloway, J., Grallert, H., Jaddoe, V., Lowe Jr, W., Roumeliotaki, T., Hattersley, A., Lindi, V., Pahkala, K., Panoutsopoulou, K., Standl, M., Flexeder, C., Bouchard, L., Aagaard Nohr, E., Marina, L., Kogevinas, M., Niinikoski, H., Dedoussis, G., Heinrich, J., Reynolds, R., Lakka, T., Zeggini, E., Raitakari, O., Chatzi, L., Inskip, H., Bustamante, M., Hivert, M., Jarvelin, M., Sørensen, T., Pennell, C., Felix, J., Jacobsson, B., Geller, F., Evans, D., Lawlor, D. (2017) Maternal and fetal genetic contribution to gestational weight gain. International Journal of Obesity, 42 (4), 775-784. doi:10.1038/ijo.2017.248

Maternal and fetal genetic contribution to gestational weight gain

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Author: Warrington, N. M.1,2; Richmond, R.3,4; Fenstra, B.5;
Organizations: 1Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia.
2Univ Western Australia, Div Obstet & Gynaecol, Perth, WA, Australia.
3Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol, Avon, England.
4Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.
5Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark.
6Norwegian Inst Publ Hlth, Oslo, Norway.
7Univ Med Ctr Rotterdam, Erasmus MC, Generat Study Grp R, Rotterdam, Netherlands.
8Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
9Erasmus MC, Univ Med Ctr Rotterdam, Dept Pediat, Rotterdam, Netherlands.
10Univ Exeter, Royal Devon & Exeter Hosp, Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England.
11Imperial Coll London, Sch Publ Hlth, Dept Publ Hlth & Primary Care, London, England.
12Univ Valencia, Univ Jaume 1, FISABIO, Epidemiol & Environm Hlth Joint Res Unit, Valencia, Spain.
13Spanish Consortium Res Epidemiol & Publ Hlth CIBE, Madrid, Spain.
14Ctr Res Environm Epidemiol CREAL, ISGlobal, Barcelona, Spain.
15IMIM Hosp Mar Med Res Inst, Barcelona, Spain.
16UPF, Barcelona, Spain.
17German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
18Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio, Finland.
19Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
20Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
21Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn,Ctr Basic Metab Res, Copenhagen, Denmark.
22Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark.
23Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu, Finland.
24Univ Munich, Med Ctr, Dr Von Hauner Childrens Hosp, Div Metab & Nutr Med, Munich, Germany.
25Univ Sherbrooke, Ctr Hosp, Ctr Rech, Sherbrooke, PQ, Canada.
26Univ Edinburgh, Queens Med Res Inst, British Heart Fdn, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
27Univ Bristol, Sch Social & Community Med, ALSPAC Children 90S, Bristol, Avon, England.
28Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark.
29Stanford Sch Med, Dept Med, Stanford, CA USA.
30Erasmus MC, Univ Med Ctr Rotterdam, Dept Internal Med, Rotterdam, Netherlands.
31Erasmus Univ, Med Ctr, Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands.
32Univ Southampton, Fac Med, Human Dev & Hlth, Southampton, Hants, England.
33Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol 2, Neuherberg, Germany.
34German Ctr Diabet Res DZD, Neuherberg, Germany.
35Helmholtz Zentrum Munchen, Clin Cooperat Grp Type Diabet 2, Neuherberg, Germany.
36Tech Univ Munich, Freising Weihenstephan, Germany.
37Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60611 USA.
38Univ Crete, Dept Social Med, Iraklion, Greece.
39Paavo Nurmi Ctr, Sports & Exercise Med Unit, Dept Hlth & Phys Act, Turku, Finland.
40Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
41Univ Sherbrooke, Fac Med & Life Sci, Dept Biochem, Sherbrooke, PQ, Canada.
42Basque Govt, Publ Hlth Div Gipuzkoa, Vitoria, Spain.
43Biodonostia, Hlth Res Inst, San Sebastian, Gipuzkoa, Spain.
44Turku Univ Hosp, Dept Pediat, Turku, Finland.
45Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
46Ludwig Maximilian Univ Munich, Univ Hosp Munich, Inst & Outpatient Clin Occupat Social & Environm, Inner City Clin, Munich, Germany.
47Univ Eastern Finland, Sch Med, Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland.
48Kuopio Res Inst Exercise Med, Kuopio, Finland.
49Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
50Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
51Maastricht Univ, Fac Hlth Med & Life Sci, Dept Genet & Cell Biol, Maastricht, Netherlands.
52Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.
53Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England.
54Barcelona Inst Sci & Technol, CRG, Barcelona, Spain.
55Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
56Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
57Univ Oulu, Bioctr Oulu, Oulu, Finland.
58Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
59Sahlgrens Acad, Dept Obstet & Gynecol, Gothenburg, Sweden.
60Inst Publ Hlth, Dept Genet & Bioinformat Domain Hlth Data & Digit, Oslo, Norway.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019050714586
Language: English
Published: Springer Nature, 2018
Publish Date: 2019-05-07
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.

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Series: International journal of obesity
ISSN: 0307-0565
ISSN-E: 1476-5497
ISSN-L: 0307-0565
Volume: 42
Issue: 4
Pages: 775 - 784
DOI: 10.1038/ijo.2017.248
OADOI: https://oadoi.org/10.1038/ijo.2017.248
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: 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). Full details of individual study and author funding, and acknowledgements, are provided in Supplementary material.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
Academy of Finland Grant Number: 285547
Detailed Information: 285547 (Academy of Finland Funding decision)
Copyright information: © 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/
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