TY - JOUR T1 - Maternal and fetal genetic contribution to gestational weight gain JF - bioRxiv DO - 10.1101/116434 SP - 116434 AU - Nicole M Warrington AU - Rebecca Richmond AU - Bjarke Fenstra AU - Ronny Myhre AU - Romy Gaillard AU - Lavinia Paternoster AU - Carol A Wang AU - Robin N Beaumont AU - Shikta Das AU - Mario Murcia AU - Sheila J Barton AU - Ana Espinosa AU - Elisabeth Theiring AU - Mustafa Atalay AU - Niina Pitkänen AU - Ioanna Ntalla AU - Anna E Jonsson AU - Rachel Freathy AU - Ville Karhunen AU - Carla MT Tiesler AU - Catherine Allard AU - Andrew Crawford AU - Susan M Ring AU - Mads Melbye AU - Per Magnus AU - Fernando Rivadeneira AU - Line Skotte AU - Torben Hansen AU - Julie Marsh AU - Mònica Guxens AU - John W Holloway AU - Harald Grallert AU - Vincent WV Jaddoe AU - William L Lowe, Jr AU - Theano Roumeliotaki AU - Andrew T Hattersley AU - Virpi Lindi AU - Katja Pahkala AU - Kalliope Panoutsopoulou AU - Marie Standl AU - Claudia Flexeder AU - Luigi Bouchard AU - Ellen Aagard Nohr AU - Loreto Santa Marina AU - Manolis Kogevinas AU - Harri Niinikoski AU - George Dedoussis AU - Joachim H Heinrich AU - Rebecca M Reynolds AU - Timo Lakka AU - Eleftheria Zeggini AU - Olli T Raitakari AU - Leda Chatzi AU - Hazel M Inskip AU - Mariona Bustamante Pineda AU - Marie-France Hivert AU - Marjo-Riitta Jarvelin AU - Thorkild IA Sørensen AU - Craig Pennell AU - Janine F Felix AU - Bo Jacobsson AU - Frank Geller AU - David M Evans AU - Debbie A Lawlor AU - Early Growth Genetics (EGG) consortium Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/14/116434.abstract N2 - 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. ER -