NLM Title Abbreviation
Hum Mol Genet
Human molecular genetics
DOI of Published Version
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.
pediactrics, cytochrome P450 3A7, high mobility group A2 protein, sex hormone, transcription factor 7 like 2, ACTL9 gene, allele, diet restriction, EBF1 gene, fetus growth, GCK gene, gene locus, genome-wide association study, genotype, glucose blood level, heredity, high birth weight, human experiment, KCNAB1 gene, L3MBTL3 gene, low birth weight, MTNR1B gene, priority journal, progeny, SH2B3 gene, single nucleotide polymorphism, uterus
Journal Article Version
Version of Record
Published Article/Book Citation
Hum Mol Genet. 2018 Feb 15;27(4):742-756. https://doi.org/10.1093/hmg/ddx429
© The Author(s) 2018
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This work is licensed under a Creative Commons Attribution 4.0 License.