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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
Author: Beaumont, Robin N.
Warrington, Nicole M.
Cavadino, Alana
Tyrrell, Jessica
Nodzenski, Michael
Horikoshi, Momoko
Geller, Frank
Myhre, Ronny
Richmond, Rebecca C.
Paternoster, Lavinia
Bradfield, Jonathan P.
Kreiner-Moller, Eskil
Huikari, Ville
Metrustry, Sarah
Lunetta, Kathryn L.
Painter, Jodie N.
Hottenga, Jouke-Jan
Allard, Catherine
Barton, Sheila J.
Espinosa Cardiel, Ana
Marsh, Julie A.
Potter, Catherine
Zhang, Ge
Ang, Wei
Berry, Diane J.
Bouchard, Luigi
Das, Shikta
Early Growth Genetics (EGG) Consortium
Hakonarson, Hakon
Heikkinen, Jani
Helgeland, Øyvind
Hocher, Berthold
Hofman, Albert
Inskip, Hazel M.
Jones, Samuel E.
Kogevinas, Manolis
Lind, Penelope A.
Marullo, Letizia
Medland, Sarah E.
Murray, Anna
Murray, Jeffrey C.
Njolstad, Pal R.
Nohr, Ellen Aagard
Reichetzeder, Christoph
Ring, Susan M.
Ruth, Katherine S.
Santa Marina, Loreto
Scholtens, Denise M.
Sebert, Sylvain
Sengpiel, Verena
Tuke, Marcus A.
Vaudel, Marc
Weedon, Michael N.
Willemsen, Gonneke
Wood, Andrew R.
Yaghootkar, Hanieh
Muglia, Louis J.
Bartels, Meike
Relton, Caroline L.
Pennell, Craig E.
Chatzi, Leda
Estivill, Xavier, 1955-
Holloway, John W.
Boomsma, Dorret I.
Montgomery, Grant W.
Murabito, Joanne M.
Spector, Tim D.
Power, Christine
Järvelin, Marjo-Ritta
Bisgaard, Hans
Grant, Struan F.
Sorensen, Thorkild I. A.
Jaddoe, Vincent W.
Jacobsson, Bo
Melbye, Mads
McCarthy, Mark I.
Hattersley, Andrew T.
Hayes, M. Geoffrey
Frayling, Timothy M.
Hivert, Marie-France
Felix, Janine F.
Hyppönen, Elina
Lowe, William L.
Evans, David M.
Lawlor, Debbie A.
Feenstra, Bjarke
Freathy, Rachel M.
Keywords: Polimorfisme genètic
Infants nadons
Genetic polymorphisms
Newborn infants
Issue Date: 3-Jan-2018
Publisher: Oxford University Press
Abstract: 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 < 5 × 10−8. 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.
Note: Reproducció del document publicat a:
It is part of: Human Molecular Genetics, 2018, vol. 27, num. 4, p. 742-756
Related resource:
ISSN: 0964-6906
Appears in Collections:Articles publicats en revistes (ISGlobal)

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