Maternal and fetal genetic contribution to gestational weight gain
Authors: Warrington Nicole M , Richmond Rebecca , Fenstra Bjarke , Myhre Ronny , Gaillard Romy , Paternoster Lavinia , Wang Carol A , Beaumont Robin N , Das Shikta , Murcia Mario , Barton Sheila J , Espinosa Ana , Theiring Elisabeth , Atalay Mustafa , Pitkänen Niina , Ntalla Ioanna , Jonsson Anna E , Freathy Rachel , Karhunen Ville , Tiesler Carla MT , Allard Catherine , Crawford Andrew , Ring Susan M , Melbye Mads , Magnus Per , Rivadeneira Fernando , Skotte Line , Hansen Torben , Marsh Julie , Guxens Mònica , Holloway John W , Grallert Harald , Jaddoe Vincent WV , Lowe William L , Roumeliotaki Theano , Hattersley Andrew T , Lindi Virpi , Pahkala Katja , Panoutsopoulou Kalliope , Standl Marie , Flexeder Claudia , Bouchard Luigi , Nohr Ellen Aagard , Santa Marina Loreto , Kogevinas Manolis , Niinikoski Harri , Dedoussis George , Heinrich Joachim H , Reynolds Rebecca M , Lakka Timo , Zeggini Eleftheria , Raitakari Olli T , Chatzi Leda , Inskip Hazel M , Bustamante Pineda Mariona , Hivert Marie-France , Jarvelin Marjo-Riitta , Sørensen Thorkild IA , Pennell Craig , Felix Janine F , Jacobsson Bo , Geller Frank , Evans David M , Lawlor Debbie A ,   Early Growth Genetics (EGG) consortium
Published: March 2017

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.