Preprint open access publication

Maternal and fetal genetic contribution to gestational weight gain

bioRxiv, Cold Spring Harbor Laboratory,

2017

DOI:10.1101/116434, Dimensions: pub.1085113107,

Authors

Murcia, Mario (9) (10)
Espinosa, Ana (10) (12) (13) (14)
Freathy, Rachel (3) (7)
Tiesler, Carla M T (15) (16)
Crawford, Andrew (3) (23)
Melbye, Mads (4) (20) (24)
Guxens, Mònica (10) (12) (13) (25)
Grallert, Harald (16) (26) (27) (28)
Pahkala, Katja (18) (31)
Santa Marina, Loreto (10) (35) (36)
Kogevinas, Manolis (10) (12) (13) (14)
Lakka, Timo (17) (40) (41)
Raitakari, Olli T (18) (37)
Inskip, Hazel M (11) (42)
Pineda, Mariona Bustamante (10) (12) (13) (43)
Jarvelin, Marjo-Riitta (8) (21) (46)
Jacobsson, Bo (48) (49)
Evans, David M * (1) (3)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Queensland, grid.1003.2
  2. (2) University of Western Australia, grid.1012.2
  3. (3) University of Bristol, grid.5337.2
  4. (4) State Serum Institute, grid.6203.7
  5. (5) Norwegian Institute of Public Health, grid.418193.6
  6. (6) Erasmus University Medical Center, grid.5645.2
  7. (7) Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, UK
  8. (8) Imperial College London, grid.7445.2
  9. (9) Epidemiology and Environmental Health Joint Research Unit, FISABIO–Universitat Jaume I–Universitat de València, Valencia, Spain
  10. (10) Institute of Health Carlos III, grid.413448.e
  11. (11) University of Southampton, grid.5491.9
  12. (12) ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
  13. (13) Pompeu Fabra University, grid.5612.0
  14. (14) Hospital Del Mar, grid.411142.3
  15. (15) Klinikum der Universität München, grid.411095.8
  16. (16) Helmholtz Zentrum München, grid.4567.0
  17. (17) University of Eastern Finland, grid.9668.1
  18. (18) University of Turku, grid.1374.1
  19. (19) Queen Mary University of London, grid.4868.2
  20. (20) University of Copenhagen, grid.5254.6, KU
  21. (21) University of Oulu, grid.10858.34
  22. (22) Centre Hospitalier Universitaire de Sherbrooke, grid.411172.0
  23. (23) University of Edinburgh, grid.4305.2
  24. (24) Stanford University, grid.168010.e
  25. (25) Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre–Sophia Children's Hospital, Rotterdam, the Netherlands
  26. (26) Friedrich Loeffler Institute, grid.417834.d
  27. (27) German Center for Diabetes Research, grid.452622.5
  28. (28) Technical University of Munich, grid.6936.a
  29. (29) Northwestern University, grid.16753.36
  30. (30) University of Crete, grid.8127.c
  31. (31) Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Health and Physical Activity, Turku, Finland
  32. (32) Wellcome Sanger Institute, grid.10306.34
  33. (33) Université de Sherbrooke, grid.86715.3d
  34. (34) University of Southern Denmark, grid.10825.3e, SDU
  35. (35) Basque Government, grid.431260.2
  36. (36) Biodonostia, grid.432380.e
  37. (37) Turku University Hospital, grid.410552.7
  38. (38) Harokopio University, grid.15823.3d
  39. (39) Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner City Clinic, University Hospital Munich, Ludwig Maximilian University of Munich, Munich, Germany
  40. (40) Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, School of Medicine, University of Eastern Finland, Kuopio, Finland
  41. (41) Kuopion Liikuntalääketieteen Tutkimuslaitos, grid.419013.e
  42. (42) University Hospital Southampton NHS Foundation Trust, grid.430506.4
  43. (43) Centre for Genomic Regulation, grid.11478.3b
  44. (44) Harvard University, grid.38142.3c
  45. (45) Massachusetts General Hospital, grid.32224.35
  46. (46) Oulu University Hospital, grid.412326.0
  47. (47) Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark
  48. (48) Department of Genetics and Bioinformatics, Domain of Health Data and Digitalization, Institute of Public Health, Oslo, Norway
  49. (49) University of Gothenburg, grid.8761.8

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 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<5×10 −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 diabetes with GWG.

Research Categories

Main Subject Area

Sustainable Development Goals

Links & Metrics

NORA University Profiles

University of Copenhagen

University of Southern Denmark

Dimensions Citation Indicators

Times Cited: 0

Field Citation Ratio (FCR): 0

Open Access Info

Green, Published