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A multi-ancestry genome-wide association study of umbilical cord insulin and c-peptide levels will form the basis of an important future bioresource

Hughes, A.E. ; Kuang, A. ; Lim, B. ; Fore, R. ; Hatem, G. LU ; Allard, C. ; Morris, A.P. ; Lawlor, D.A. ; Beaumont, R.N. and Lowe, W.L. , et al. (2022) In Diabetic Medicine: A journal of the British Diabetic Association 39(SUPPL 1).
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
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
in
Diabetic Medicine: A journal of the British Diabetic Association
volume
39
issue
SUPPL 1
article number
P50
publisher
Wiley-Blackwell
ISSN
1464-5491
DOI
10.1111/dme.14809
language
English
LU publication?
yes
additional info
M1 - (Hughes A.E.; Lim B.; Beaumont R.N.; Freathy R.) Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom M1 - (Kuang A.; Lowe W.L.) Department of Medicine, Northwestern University, Chicago, IL, United States M1 - (Fore R.; Hivert W.-F.) Department of Population Medicine, Harvard Pilgrim Healthcare Institute, Boston, MA, United States M1 - (Hatem G.; Prashad R.) Department of Clinical Sciences, Lund University Diabetes Centre, Malmo, Sweden M1 - (Allard C.) Centre de Recherche, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada M1 - (Morris A.P.) Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, United Kingdom M1 - (Lawlor D.A.) MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom M1 - (Lawlor D.A.) Population Health Sciences, Bristol Medical School, Bristol, United Kingdom
id
da3164e9-25aa-4759-adfe-29485fee000a
alternative location
https://www.embase.com/search/results?subaction=viewrecord&id=L638056431&from=export
date added to LUP
2026-05-22 08:50:30
date last changed
2026-05-22 08:50:30
@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 &lt; 5 × 10-8) or suggestive (P &lt; 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}},
}