Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111887
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dc.contributor.authorBeaumont, R.en
dc.contributor.authorWarrington, N.en
dc.contributor.authorCavadino, A.en
dc.contributor.authorTyrrell, J.en
dc.contributor.authorNodzenski, M.en
dc.contributor.authorHorikoshi, M.en
dc.contributor.authorGeller, F.en
dc.contributor.authorMyhre, R.en
dc.contributor.authorRichmond, R.en
dc.contributor.authorPaternoster, L.en
dc.contributor.authorBradfield, J.en
dc.contributor.authorKreiner-Møller, E.en
dc.contributor.authorHuikari, V.en
dc.contributor.authorMetrustry, S.en
dc.contributor.authorLunetta, K.en
dc.contributor.authorPainter, J.en
dc.contributor.authorHottenga, J.en
dc.contributor.authorAllard, C.en
dc.contributor.authorBarton, S.en
dc.contributor.authorEspinosa, A.en
dc.contributor.authoret al.en
dc.date.issued2018en
dc.identifier.citationHuman Molecular Genetics, 2018; 27(4):742-756en
dc.identifier.issn0964-6906en
dc.identifier.issn1460-2083en
dc.identifier.urihttp://hdl.handle.net/2440/111887-
dc.description.abstractGenome-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.en
dc.description.statementofresponsibilityRobin N Beaumont, Nicole M Warrington, Alana Cavadino, Jessica Tyrrell, Michael Nodzenski … Deborah Lawlor … et al.en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.rights© The Author(s) . Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectEarly Growth Genetics (EGG) Consortiumen
dc.titleGenome-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 geneticsen
dc.typeJournal articleen
dc.identifier.rmid0030085913en
dc.identifier.doi10.1093/hmg/ddx429en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1104818en
dc.relation.granthttp://purl.org/au-research/grants/arc/FT130101709en
dc.relation.granthttp://purl.org/au-research/grants/arc/FT110100548en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/613667en
dc.identifier.pubid392678-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.library.teamDS10en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Molecular and Biomedical Science publications

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