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

doi:10.1016/j.diabet.2017.03.002

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 journal › Article › peer-review

21 Scopus citations

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 language	English (US)
Pages (from-to)	323-331
Number of pages	9
Journal	Diabetes and Metabolism
Volume	43
Issue number	4
DOIs	https://doi.org/10.1016/j.diabet.2017.03.002
State	Published - Sep 2017

Keywords

Gestational diabetes
KCNQ1
Meta-analysis
Placenta

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.diabet.2017.03.002

Cite this

@article{36d4995d13db44fd8b45d4d0d6643f82,

title = "Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations",

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.",

keywords = "Gestational diabetes, KCNQ1, Meta-analysis, Placenta",

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.}",

note = "Funding Information: This work was supported by the Evelyn Trust (grant number EW9035322 ); Diabetes UK (grant number 11/0004241 ); the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK ) (grant number RG1644 ); the Medical Research Council (grant number 7500001180 ); European Union Framework 5 (grant number QLK4-1999-01422 ); the Mothercare Charitable Foundation (grant number RG54608 ); Newlife Foundation for Disabled Children (grant number 07/20 ); the World Cancer Research Fund International (grant number 2004/03 ); and the National Institute for Health Research Cambridge Biomedical Research Centre. The HAPO Study work was supported by the National Institutes of Health (grant numbers HD-34242 , HD-34243 , HG-004415 , and CA-141688 ); the Institutes of Health Research–INMD (grant number 110791 ); and by the American Diabetes Association. The placental expression work described in this manuscript was performed at Cambridge Genomic Services at the Department of Pathology, University of Cambridge and the authors are grateful for gaining access to the necessary equipment there. The authors acknowledge the excellent technical assistance in the laboratory for this project that was provided by Dianne Wingate, Rachel Seear and Radka Platte. The authors would like to thank all the families that took part in the Cambridge Baby Growth Study, and acknowledge the crucial role played by the research nurses especially Suzanne Smith, Ann-Marie Wardell and Karen Forbes, staff at the Addenbrooke's Wellcome Trust Clinical Research Facility, and midwives at the Rosie Maternity Hospital in collecting data for this study. The authors would also like to thank Dr. Felix Day, of the Medical Research Council Epidemiology Unit at the University of Cambridge for helpful discussions about the manuscript. Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = sep,

doi = "10.1016/j.diabet.2017.03.002",

language = "English (US)",

volume = "43",

pages = "323--331",

journal = "Diabetes and Metabolism",

issn = "1262-3636",

publisher = "Elsevier Masson",

number = "4",

}

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.

N1 - Funding Information: This work was supported by the Evelyn Trust (grant number EW9035322 ); Diabetes UK (grant number 11/0004241 ); the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK ) (grant number RG1644 ); the Medical Research Council (grant number 7500001180 ); European Union Framework 5 (grant number QLK4-1999-01422 ); the Mothercare Charitable Foundation (grant number RG54608 ); Newlife Foundation for Disabled Children (grant number 07/20 ); the World Cancer Research Fund International (grant number 2004/03 ); and the National Institute for Health Research Cambridge Biomedical Research Centre. The HAPO Study work was supported by the National Institutes of Health (grant numbers HD-34242 , HD-34243 , HG-004415 , and CA-141688 ); the Institutes of Health Research–INMD (grant number 110791 ); and by the American Diabetes Association. The placental expression work described in this manuscript was performed at Cambridge Genomic Services at the Department of Pathology, University of Cambridge and the authors are grateful for gaining access to the necessary equipment there. The authors acknowledge the excellent technical assistance in the laboratory for this project that was provided by Dianne Wingate, Rachel Seear and Radka Platte. The authors would like to thank all the families that took part in the Cambridge Baby Growth Study, and acknowledge the crucial role played by the research nurses especially Suzanne Smith, Ann-Marie Wardell and Karen Forbes, staff at the Addenbrooke's Wellcome Trust Clinical Research Facility, and midwives at the Rosie Maternity Hospital in collecting data for this study. The authors would also like to thank Dr. Felix Day, of the Medical Research Council Epidemiology Unit at the University of Cambridge for helpful discussions about the manuscript. Publisher Copyright: © 2017 The Authors

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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DO - 10.1016/j.diabet.2017.03.002

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SN - 1262-3636

VL - 43

SP - 323

EP - 331

JO - Diabetes and Metabolism

JF - Diabetes and Metabolism

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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Research data supporting "Associations between a Fetal Imprinted Gene Allele Score and Late Pregnancy Maternal Glucose Concentrations"

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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Fingerprint

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Research data supporting "Associations between a Fetal Imprinted Gene Allele Score and Late Pregnancy Maternal Glucose Concentrations"

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