Author:
|
Warrington, Nicole M.; Richmond, Rebecca C.; Fenstra, Bjarke; Myhre, Ronny; Gaillard, Romy; Paternoster, Lavinia; Wang, Carol A.; Beaumont, Robin N.; Das, Shikta; Murcia, Mario; Barton, Sheila J.; Espinosa Cardiel, Ana; Thiering, Elisabeth; Atalay, Mustafa; Pitkanen, Niina; Ntalla, Ioanna; Jonsson, Anna E.; Freathy, Rachel M.; Karhunen, Ville; Tiesler, Carla M. T.; Allard, Catherine; Crawford, Andrew; Ring, Susan M.; Melbye, Mads; Magnus, Per; Rivadeneira, Fernando; Skotte, Line; Hansen, Torben; Marsh, Julie A.; Guxens, Mònica; Holloway, John W.; Grallert, Harald; Jaddoe, Vincent W.; Lowe, William L.; Roumeliotaki, Theano; Hattersley, Andrew T.; Lindi, Virpi; Pahkala, Katja; Panoutsopoulou, Kalliope; Standl, Marie; Flexeder, Claudia; Bouchard, Luigi; Nohr, Ellen Aagard; Marina, Loreto Santa; Kogevinas, Manolis; Niinikoski, Harri; Dedoussis, George; Heinrich, Joachim; Reynolds, Rebecca M.; Lakka, Timo; Zeggini, Eleftheria; Raitakari, Olli T.; Chatzi, Leda; Inskip, Hazel M.; Bustamante Pineda, Mariona; Hivert, Marie-France; Jarvelin, Marjo-Riitta; Sorensen, Thorkild I. A.; Pennell, Craig E.; Felix, Janine F.; Jacobsson, Bo; Geller, Frank; Evans, David M.; Lawlor, Debbie A.
|
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 (e.g.
maternal BMI and glucose, birthweight). 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 explaining variation in GWG. Variants near the
Pregnancy Specific Beta-1-Glycoprotein 5 (PSG5) gene reached
genome-wide significance (P=1.71 x 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
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.International Journal of Obesity accepted article preview
online, 09 October 2017. doi:10.1038/ijo.2017.248. |