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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620597
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
Authors:
Beaumont, R. N. [et al]; Hattersley, Andrew T.
Abstract:
Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while 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<5x10−8. 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 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
Citation:
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. 3 Jan 2018. Human Molecular Genetics
Publisher:
Oxford Journals
Journal:
Human Molecular Genetics
Issue Date:
3-Jan-2018
URI:
http://hdl.handle.net/11287/620597
DOI:
10.1093/hmg/ddx429
Additional Links:
http://fdslive.oup.com/www.oup.com/pdf/production_in_progress.pdf
Note:
This article is freely available from the publisher's site. Click on the Additional Link above to access it.
Type:
Journal Article
Language:
en
ISSN:
0964-6906; 1460-2083
Appears in Collections:
Diabetes/Endocrine Services; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorBeaumont, R. N. [et al]en
dc.contributor.authorHattersley, Andrew T.en
dc.date.accessioned2018-01-11T09:56:42Z-
dc.date.available2018-01-11T09:56:42Z-
dc.date.issued2018-01-03-
dc.identifier.citationGenome-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. 3 Jan 2018. Human Molecular Geneticsen
dc.identifier.issn0964-6906-
dc.identifier.issn1460-2083-
dc.identifier.doi10.1093/hmg/ddx429-
dc.identifier.urihttp://hdl.handle.net/11287/620597-
dc.description.abstractGenome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while 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<5x10−8. 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 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 weightsen
dc.language.isoenen
dc.publisherOxford Journalsen
dc.relation.urlhttp://fdslive.oup.com/www.oup.com/pdf/production_in_progress.pdfen
dc.rightsArchived with thanks to Human Molecular Geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
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.journalHuman Molecular Geneticsen
dc.description.noteThis article is freely available from the publisher's site. Click on the Additional Link above to access it.en
dc.type.versionIn press (epub ahead of print)en
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