title: Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics
Creators: name: Beaumont, Robin N.
name: Warrington, Nicole M.
name: Cavadino, Alana
name: Tyrrell, Jessica
name: Nodzenski, Michael
name: Horikoshi, Momoko
name: Geller, Frank
name: Myhre, Ronny
name: Richmond, Rebecca C.
name: Paternoster, Lavinia
name: Bradfield, Jonathan P.
name: Kreiner-Møller, Eskil
name: Huikari, Ville
name: Metrustry, Sarah
name: Lunetta, Kathryn L.
name: Painter, Jodie N.
name: Hottenga, Jouke-Jan
name: Allard, Catherine
name: Barton, Sheila J.
name: Espinosa, Ana
name: Marsh, Julie A.
name: Potter, Catherine
name: Zhang, Ge
name: Ang, Wei
name: Berry, Diane J.
name: Bouchard, Luigi
name: Das, Shikta
name: Hakonarson, Hakon
name: Heikkinen, Jani
name: Helgeland, Øyvind
name: Hocher, Berthold
name: Hofman, Albert
name: Inskip, Hazel M.
name: Jones, Samuel E.
name: Kogevinas, Manolis
name: Lind, Penelope A.
name: Marullo, Letizia
name: Medland, Sarah E.
name: Murray, Anna
name: Murray, Jeffrey C.
name: Njølstad, Pa ̊l R.
name: Nohr, Ellen A.
name: Reichetzeder, Christoph
name: Ring, Susan M.
name: Ruth, Katherine S.
name: Santa-Marina, Loreto
name: Scholtens, Denise M.
name: Sebert, Sylvain
name: Sengpiel, Verena
name: Tuke, Marcus A.
name: Vaudel, Marc
name: Weedon, Michael N.
name: Willemsen, Gonneke
name: Wood, Andrew R.
name: Yaghootkar, Hanieh
name: Muglia, Louis J.
name: Bartels, Meike
name: Relton, Caroline L.
name: Pennell, Craig E.
name: Chatzi, Leda
name: Estivill, Xavier
name: Holloway, John W.
name: Boomsma, Dorret I.
name: Montgomery, Grant W.
name: Murabito, Joanne M.
name: Spector, Tim D.
name: Power, Christine
name: Ja ̈rvelin, Marjo-Ritta
name: Bisgaard, Hans
name: Grant, Struan F.A.
name: Sørensen, Thorkild I.A.
name: Jaddoe, Vincent W.
name: Jacobsson, Bo
name: Melbye, Mads
name: McCarthy, Mark I.
name: Hattersley, Andrew T.
name: Hayes, M. Geoffrey
name: Frayling, Timothy M.
name: Hivert, Marie-France
name: Felix, Janine F.
name: Hyppo ̈nen, Elina
name: Lowe, William L. , Jr
name: Evans, David M.
name: Lawlor, Debbie A.
name: Feenstra, Bjarke
name: Freathy, Rachel M.
Publisher: name: Universität Potsdam
Year: 2019

description: Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P &lt; 5 Â 10 À8 . In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
description: Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, 628