Maternal and fetal genetic contribution to gestational weight gain

N M Warrington^{1

2}, R Richmond^{3

4}, B Fenstra⁵, R Myhre⁶, R Gaillard^{7

8

9}, L Paternoster^{3

4}, C A Wang², R N Beaumont¹⁰, S Das¹¹, M Murcia^{12

13}, S J Barton¹⁴, A Espinosa^{13

15

16

17}, E Thiering^{18

19}, M Atalay²⁰, N Pitkänen²¹, I Ntalla²², A E Jonsson²³, R Freathy^{3

10}, V Karhunen^{24

25}, C M T Tiesler^{18

19}, C Allard²⁶, A Crawford^{3

27}, S M Ring^{3

28}, M Melbye^{5

29

30}, P Magnus⁶, F Rivadeneira^{7

8

31}, L Skotte⁵, T Hansen²³, J Marsh², M Guxens^{13

15

17

32}, J W Holloway³³, H Grallert^{34

35

36

37

38}, V W V Jaddoe^{7

8

9}, W L Lowe Jr³⁹, T Roumeliotaki⁴⁰, A T Hattersley¹⁰, V Lindi²⁰, K Pahkala^{21

41}, K Panoutsopoulou⁴², M Standl¹⁸, C Flexeder¹⁸, L Bouchard⁴³, E Aagaard Nohr⁴⁴, L Santa Marina^{13

45

46}, M Kogevinas^{13

15

16

17}, H Niinikoski⁴⁷, G Dedoussis⁴⁸, J Heinrich^{18

49}, R M Reynolds²⁷, T Lakka^{20

50

51}, E Zeggini⁴², O T Raitakari^{21

52}, L Chatzi^{40

53

40

54}, H M Inskip^{14

55}, M Bustamante^{13

15

17

56}, M-F Hivert^{57

58}, M-R Jarvelin^{24

25

59

60}, T I A Sørensen^{23

61}, C Pennell², J F Felix^{7

8

9}, B Jacobsson^{62

63}, F Geller⁵, D M Evans^{1

3}, D A Lawlor^{3

4}

Affiliations

¹ University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
² Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia.
³ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
⁴ Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
⁵ Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
⁶ Norwegian Institute of Public Health, Oslo, Norway.
⁷ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁸ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁹ Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁰ Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter, UK.
¹¹ Department of Public Health and Primary Care, School of Public Health, Imperial College London, London, UK.
¹² Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain.
¹³ Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain.
¹⁴ MRC Lifecourse Epidemiology Unit, Faulty of Medicine, University of Southampton, Southampton, UK.
¹⁵ ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
¹⁶ IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
¹⁷ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
¹⁸ Institute of Epidemiology I, Helmholtz Zentrum München- German Research Center for Environmental Health, Neuherberg, Germany.
¹⁹ Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany.
²⁰ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
²¹ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
²² William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
²³ The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²⁴ Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
²⁵ Biocenter Oulu, University of Oulu, Oulu, Finland.
²⁶ Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada.
²⁷ British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
²⁸ ALSPAC (Children of the 90s), School of Social and Community Medicine, University of Bristol, Bristol, UK.
²⁹ Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark.
³⁰ Department of Medicine, Stanford School of Medicine, Stanford, CA, USA.
³¹ Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³² Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.
³³ Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
³⁴ Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.
³⁵ German Center for Diabetes Research (DZD), Neuherberg, Germany.
³⁶ Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
³⁷ Clinical Cooperation Group Nutrigenomics and Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
³⁸ Technische Universität München, Freising, Germany.
³⁹ Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁴⁰ Department of Social Medicine, University of Crete, Crete, Greece.
⁴¹ Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Health and Physical Activity, Turku, Finland.
⁴² Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
⁴³ Department of Biochemistry, Faculty of medicine and life sciences, Université de Sherbrooke, Sherbrooke, Canada.
⁴⁴ Public Health Division of Gipuzkoa, Basque Government, Vitoria-Gasteiz, Spain.
⁴⁵ Health Research Institute, Biodonostia, San Sebastián, Gipuzkoa, Spain.
⁴⁶ Health Research Institute, Biodonostia, San Sebastián, Spain.
⁴⁷ Department of Pediatrics, Turku University Hospital, Turku, Finland.
⁴⁸ Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece.
⁴⁹ Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner City Clinic, University Hospital Munich, Ludwig Maximilian University of Munich, Munich, Germany.
⁵⁰ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, School of Medicine, University of Eastern Finland, Kuopio, Finland.
⁵¹ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
⁵² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁵³ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁵⁴ Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
⁵⁵ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁵⁶ Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
⁵⁷ Department of Population Medicine at Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA.
⁵⁸ Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
⁵⁹ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
⁶⁰ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
⁶¹ Department of Clinical Epidemiology (formally the Institute of Preventive Medicine), Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
⁶² Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
⁶³ Department of Genetics and Bioinformatics, Domain of Health Data and Digitalization, Institute of Public Health, Oslo, Norway.

PMID: 28990592
PMCID: PMC5784805
DOI: 10.1038/ijo.2017.248

Maternal and fetal genetic contribution to gestational weight gain

N M Warrington et al. Int J Obes (Lond). 2018 Apr.

. 2018 Apr;42(4):775-784.

doi: 10.1038/ijo.2017.248. Epub 2017 Oct 9.

Authors

Affiliations

¹ University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
² Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia.
³ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
⁴ Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
⁵ Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
⁶ Norwegian Institute of Public Health, Oslo, Norway.
⁷ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁸ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁹ Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁰ Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter, UK.
¹¹ Department of Public Health and Primary Care, School of Public Health, Imperial College London, London, UK.
¹² Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain.
¹³ Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain.
¹⁴ MRC Lifecourse Epidemiology Unit, Faulty of Medicine, University of Southampton, Southampton, UK.
¹⁵ ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
¹⁶ IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
¹⁷ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
¹⁸ Institute of Epidemiology I, Helmholtz Zentrum München- German Research Center for Environmental Health, Neuherberg, Germany.
¹⁹ Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany.
²⁰ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
²¹ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
²² William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
²³ The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²⁴ Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
²⁵ Biocenter Oulu, University of Oulu, Oulu, Finland.
²⁶ Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada.
²⁷ British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
²⁸ ALSPAC (Children of the 90s), School of Social and Community Medicine, University of Bristol, Bristol, UK.
²⁹ Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark.
³⁰ Department of Medicine, Stanford School of Medicine, Stanford, CA, USA.
³¹ Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³² Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.
³³ Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
³⁴ Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.
³⁵ German Center for Diabetes Research (DZD), Neuherberg, Germany.
³⁶ Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
³⁷ Clinical Cooperation Group Nutrigenomics and Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
³⁸ Technische Universität München, Freising, Germany.
³⁹ Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁴⁰ Department of Social Medicine, University of Crete, Crete, Greece.
⁴¹ Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Health and Physical Activity, Turku, Finland.
⁴² Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
⁴³ Department of Biochemistry, Faculty of medicine and life sciences, Université de Sherbrooke, Sherbrooke, Canada.
⁴⁴ Public Health Division of Gipuzkoa, Basque Government, Vitoria-Gasteiz, Spain.
⁴⁵ Health Research Institute, Biodonostia, San Sebastián, Gipuzkoa, Spain.
⁴⁶ Health Research Institute, Biodonostia, San Sebastián, Spain.
⁴⁷ Department of Pediatrics, Turku University Hospital, Turku, Finland.
⁴⁸ Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece.
⁴⁹ Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner City Clinic, University Hospital Munich, Ludwig Maximilian University of Munich, Munich, Germany.
⁵⁰ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, School of Medicine, University of Eastern Finland, Kuopio, Finland.
⁵¹ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
⁵² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁵³ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁵⁴ Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
⁵⁵ NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁵⁶ Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
⁵⁷ Department of Population Medicine at Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA.
⁵⁸ Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
⁵⁹ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
⁶⁰ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
⁶¹ Department of Clinical Epidemiology (formally the Institute of Preventive Medicine), Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
⁶² Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
⁶³ Department of Genetics and Bioinformatics, Domain of Health Data and Digitalization, Institute of Public Health, Oslo, Norway.

PMID: 28990592
PMCID: PMC5784805
DOI: 10.1038/ijo.2017.248

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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Conflict of interest statement

DAL has received support from Roche Diagnostics and Medronic Ltd for biomarker research unrelated to this study. HMI and SJB have received research funding from Abbott Nutrition, Nestec and Danone Nutricia, for research unrelated to this study. The remaining authors declare no conflict of interest.

References

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Maternal and fetal genetic contribution to gestational weight gain

Affiliations

Maternal and fetal genetic contribution to gestational weight gain

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources