@misc{da3164e9-25aa-4759-adfe-29485fee000a,
  abstract     = {{Aims: Fetal insulin is a key regulator of fetal growth and the major contributor to high birth weight in pregnancies with maternal diabetes. There is evidence for genetic variation in regulating fetal insulin, but this has not been studied on a large-scale. We performed a genome-wide association study (GWAS) of umbilical cord insulin and c-peptide measurements to identify genetic variants associated with fetal insulin levels and interrogate relationships with glycaemic traits and birth weight. Methods: We included women and offspring from term pregnancies of diverse ancestry (six international studies). We performed a multi-ancestry meta-analysis of umbilical cord insulin (n = 5,134 maternal samples, n = 5,429 fetal samples) and c-peptide (n = 5,871 maternal samples, n = 5,201 fetal samples). We explored relationships with maternal and fetal SNPs known to be associated with fasting plasma glucose (FPG), insulin secretion, and glycaemic traits and birth weight. Results: No SNPs of genome-wide (P < 5 × 10-8) or suggestive (P < 1 × 10-5) significance were identified. There was no enrichment of associations for SNPs associated with FPG, insulin secretion or glycaemic traits and birth weight. However, pooled genetic effects had expected directional associations; e.g. pooled over 91 FPG SNPs, there was a 0.004 (95% CI -0.001- 0.008) SD higher umbilical cord insulin/c-peptide per maternal FPG-raising allele. Conclusions: This was the first GWAS of an umbilical cord biomarker and although the maximum number of available samples was included, it was underpowered to detect important associations between maternal-fetal genotypes and fetal insulin levels. However, additional samples will be added to develop this bioresource and explore important questions relating to fetal insulin.}},
  author       = {{Hughes, A.E. and Kuang, A. and Lim, B. and Fore, R. and Hatem, G. and Allard, C. and Morris, A.P. and Lawlor, D.A. and Beaumont, R.N. and Lowe, W.L. and Hivert, W.-F. and Prashad, R. and Freathy, R.}},
  issn         = {{1464-5491}},
  keywords     = {{biological marker; C peptide; endogenous compound; insulin; allele; birth weight; conference abstract; controlled study; female; fetus; gene expression; gene frequency; genetic marker; genetic variability; genome-wide association study; genotype; glucose blood level; heredity; human; human tissue; insulin blood level; insulin release; meta analysis; pregnancy; progeny; single nucleotide polymorphism; umbilical cord}},
  language     = {{eng}},
  note         = {{Conference Abstract}},
  number       = {{SUPPL 1}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Diabetic Medicine: A journal of the British Diabetic Association}},
  title        = {{A multi-ancestry genome-wide association study of umbilical cord insulin and c-peptide levels will form the basis of an important future bioresource}},
  url          = {{http://dx.doi.org/10.1111/dme.14809}},
  doi          = {{10.1111/dme.14809}},
  volume       = {{39}},
  year         = {{2022}},
}