@article{7b93a96368ab445eaddbaabfa8863395,
title = "Fetal genotype and maternal glucose have independent and additive effects on birth weight",
abstract = "Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry (n = 2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics has a major impact on fetal growth and acts predominantly through independent mechanisms.",
author = "Hughes, {Alice E.} and Michael Nodzenski and Beaumont, {Robin N.} and Octavious Talbot and Shields, {Beverley M.} and Scholtens, {Denise M.} and Knight, {Bridget A.} and {>William Lowe}, {W. L.L.} and Hattersley, {Andrew T.} and Freathy, {Rachel M.}",
note = "Funding Information: Acknowledgments. We acknowledge the work of the EFSOCH and HAPO investigators, whose names can be viewed in their original publications (1,9). We acknowledge the role of all professionals and families who contributed to EFSOCH and HAPO. Funding. A.E.H. was an Academic Foundation Year 2 Doctor funded by the National Institute for Health Research (NIHR). R.N.B. and R.M.F. are funded by the Wellcome Trust and Royal Society, grant 104150/Z/14/Z. A.T.H. is a Wellcome Trust Senior Investigator and an NIHR Senior Investigator. EFSOCH was supported by South West National Health Service (NHS) Research and Development, Exeter NHS Research and Development, the Darlington Trust, and the Peninsula NIHR Clinical Research Facility at the University of Exeter. Genotyping of the EFSOCH study samples was funded by the Wellcome Trust and Royal Society, grant 104150/Z/ 14/Z. HAPO was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Research Resources, and the American Diabetes Association. Publisher Copyright: {\textcopyright} 2018 by the American Diabetes Association.",
year = "2018",
month = may,
day = "1",
doi = "10.2337/db17-1188",
language = "English (US)",
volume = "67",
pages = "1024--1029",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "5",
}
