Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

C. J. Petry*, K. Mooslehner, P. Prentice, M. G. Hayes, M. Nodzenski, D. M. Scholtens, I. A. Hughes, C. L. Acerini, K. K. Ong, W. L. Lowe, D. B. Dunger

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Aim We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy. Methods In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios). Results Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10–4) and INS rs2585 (P-value = 7 × 10–4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10–3) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10–3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10–6, n = 981, r2 = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10–3, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10–8, rs2585, P-value = 3.6 × 10–5) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10–8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2). Conclusion This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.

Original languageEnglish (US)
Pages (from-to)323-331
Number of pages9
JournalDiabetes and Metabolism
Volume43
Issue number4
DOIs
StatePublished - Sep 2017

Fingerprint

Alleles
Mothers
Glucose
Pregnancy
Single Nucleotide Polymorphism
Genes
Gestational Diabetes
Pregnancy Outcome
Hyperglycemia
Meta-Analysis
Odds Ratio
Outcome Assessment (Health Care)
Genome
DNA
Growth

Keywords

  • Gestational diabetes
  • KCNQ1
  • Meta-analysis
  • Placenta

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Petry, C. J. ; Mooslehner, K. ; Prentice, P. ; Hayes, M. G. ; Nodzenski, M. ; Scholtens, D. M. ; Hughes, I. A. ; Acerini, C. L. ; Ong, K. K. ; Lowe, W. L. ; Dunger, D. B. / Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations. In: Diabetes and Metabolism. 2017 ; Vol. 43, No. 4. pp. 323-331.
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abstract = "Aim We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy. Methods In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios). Results Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10–4) and INS rs2585 (P-value = 7 × 10–4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10–3) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10–3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10–6, n = 981, r2 = 2.0{\%}) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10–3, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10–8, rs2585, P-value = 3.6 × 10–5) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10–8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2). Conclusion This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.",
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author = "Petry, {C. J.} and K. Mooslehner and P. Prentice and Hayes, {M. G.} and M. Nodzenski and Scholtens, {D. M.} and Hughes, {I. A.} and Acerini, {C. L.} and Ong, {K. K.} and Lowe, {W. L.} and Dunger, {D. B.}",
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Petry, CJ, Mooslehner, K, Prentice, P, Hayes, MG, Nodzenski, M, Scholtens, DM, Hughes, IA, Acerini, CL, Ong, KK, Lowe, WL & Dunger, DB 2017, 'Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations', Diabetes and Metabolism, vol. 43, no. 4, pp. 323-331. https://doi.org/10.1016/j.diabet.2017.03.002

Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations. / Petry, C. J.; Mooslehner, K.; Prentice, P.; Hayes, M. G.; Nodzenski, M.; Scholtens, D. M.; Hughes, I. A.; Acerini, C. L.; Ong, K. K.; Lowe, W. L.; Dunger, D. B.

In: Diabetes and Metabolism, Vol. 43, No. 4, 09.2017, p. 323-331.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

AU - Petry, C. J.

AU - Mooslehner, K.

AU - Prentice, P.

AU - Hayes, M. G.

AU - Nodzenski, M.

AU - Scholtens, D. M.

AU - Hughes, I. A.

AU - Acerini, C. L.

AU - Ong, K. K.

AU - Lowe, W. L.

AU - Dunger, D. B.

PY - 2017/9

Y1 - 2017/9

N2 - Aim We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy. Methods In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios). Results Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10–4) and INS rs2585 (P-value = 7 × 10–4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10–3) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10–3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10–6, n = 981, r2 = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10–3, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10–8, rs2585, P-value = 3.6 × 10–5) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10–8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2). Conclusion This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.

AB - Aim We hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy. Methods In the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios). Results Four fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10–4) and INS rs2585 (P-value = 7 × 10–4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10–3) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10–3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10–6, n = 981, r2 = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10–3, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10–8, rs2585, P-value = 3.6 × 10–5) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10–8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2). Conclusion This study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.

KW - Gestational diabetes

KW - KCNQ1

KW - Meta-analysis

KW - Placenta

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