Maternal gestational diabetes mellitus and newborn DNA Methylation: Findings from the pregnancy and childhood epigenetics consortium

Caitlin G. Howe; Bianca Cox; Ruby Fore; James Jungius; Tuomas Kvist; Samantha Lent; Harriet E. Miles; Lucas A. Salas; Sheryl Rifas-Shiman; Anne P. Starling; Paul Yousefi; Christine Ladd-Acosta; Andrea Baccarelli; Elisabeth B. Binder; Vaia Lida Chatzi; Darina Czamara; Dana Dabelea; Dawn L. DeMeo; Akram Ghantous; Zdenko Herceg; Eero Kajantie; Jari M.T. Lahti; Debbie A. Lawlor; Augusto Litonjua; Tim S. Nawrot; Ellen A. Nohr; Emily Oken; Costanza Pizzi; Michelle Plusquin; Katri Räikkönen; Caroline L. Relton; Gemma C. Sharp; Thorkild I.A. Sørensen; Jordi Sunyer; Martine Vrijheid; Weiming Zhang; Marie France Hivert; Carrie V. Breton

doi:10.2337/dc19-0524

Maternal gestational diabetes mellitus and newborn DNA Methylation: Findings from the pregnancy and childhood epigenetics consortium

Caitlin G. Howe, Bianca Cox, Ruby Fore, James Jungius, Tuomas Kvist, Samantha Lent, Harriet E. Miles, Lucas A. Salas, Sheryl Rifas-Shiman, Anne P. Starling, Paul Yousefi, Christine Ladd-Acosta, Andrea Baccarelli, Elisabeth B. Binder, Vaia Lida Chatzi, Darina Czamara, Dana Dabelea, Dawn L. DeMeo, Akram Ghantous, Zdenko HercegEero Kajantie, Jari M.T. Lahti, Debbie A. Lawlor, Augusto Litonjua, Tim S. Nawrot, Ellen A. Nohr, Emily Oken, Costanza Pizzi, Michelle Plusquin, Katri Räikkönen, Caroline L. Relton, Gemma C. Sharp, Thorkild I.A. Sørensen, Jordi Sunyer, Martine Vrijheid, Weiming Zhang, Marie France Hivert, Carrie V. Breton

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-Analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, usingDNAmethylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations betweenGDMandDNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-Analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene bodyof CYP2E1. IndividualCpGanalyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS MaternalGDMwas associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.

Original language	English (US)
Pages (from-to)	98-105
Number of pages	8
Journal	Diabetes care
Volume	43
Issue number	1
DOIs	https://doi.org/10.2337/dc19-0524
State	Published - Jan 1 2020

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Advanced and Specialized Nursing

Access to Document

10.2337/dc19-0524

Cite this

Howe, C. G., Cox, B., Fore, R., Jungius, J., Kvist, T., Lent, S., Miles, H. E., Salas, L. A., Rifas-Shiman, S., Starling, A. P., Yousefi, P., Ladd-Acosta, C., Baccarelli, A., Binder, E. B., Chatzi, V. L., Czamara, D., Dabelea, D., DeMeo, D. L., Ghantous, A., ... Breton, C. V. (2020). Maternal gestational diabetes mellitus and newborn DNA Methylation: Findings from the pregnancy and childhood epigenetics consortium. Diabetes care, 43(1), 98-105. https://doi.org/10.2337/dc19-0524

Howe, CG, Cox, B, Fore, R, Jungius, J, Kvist, T, Lent, S, Miles, HE, Salas, LA, Rifas-Shiman, S, Starling, AP, Yousefi, P, Ladd-Acosta, C, Baccarelli, A, Binder, EB, Chatzi, VL, Czamara, D, Dabelea, D, DeMeo, DL, Ghantous, A, Herceg, Z, Kajantie, E, Lahti, JMT, Lawlor, DA, Litonjua, A, Nawrot, TS, Nohr, EA, Oken, E, Pizzi, C, Plusquin, M, Räikkönen, K, Relton, CL, Sharp, GC, Sørensen, TIA, Sunyer, J, Vrijheid, M, Zhang, W, Hivert, MF & Breton, CV 2020, 'Maternal gestational diabetes mellitus and newborn DNA Methylation: Findings from the pregnancy and childhood epigenetics consortium', Diabetes care, vol. 43, no. 1, pp. 98-105. https://doi.org/10.2337/dc19-0524

@article{9dc4183639824a7b9e58912adc5a5113,

title = "Maternal gestational diabetes mellitus and newborn DNA Methylation: Findings from the pregnancy and childhood epigenetics consortium",

abstract = "OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-Analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, usingDNAmethylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations betweenGDMandDNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-Analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene bodyof CYP2E1. IndividualCpGanalyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS MaternalGDMwas associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.",

author = "Howe, {Caitlin G.} and Bianca Cox and Ruby Fore and James Jungius and Tuomas Kvist and Samantha Lent and Miles, {Harriet E.} and Salas, {Lucas A.} and Sheryl Rifas-Shiman and Starling, {Anne P.} and Paul Yousefi and Christine Ladd-Acosta and Andrea Baccarelli and Binder, {Elisabeth B.} and Chatzi, {Vaia Lida} and Darina Czamara and Dana Dabelea and DeMeo, {Dawn L.} and Akram Ghantous and Zdenko Herceg and Eero Kajantie and Lahti, {Jari M.T.} and Lawlor, {Debbie A.} and Augusto Litonjua and Nawrot, {Tim S.} and Nohr, {Ellen A.} and Emily Oken and Costanza Pizzi and Michelle Plusquin and Katri R{\"a}ikk{\"o}nen and Relton, {Caroline L.} and Sharp, {Gemma C.} and S{\o}rensen, {Thorkild I.A.} and Jordi Sunyer and Martine Vrijheid and Weiming Zhang and Hivert, {Marie France} and Breton, {Carrie V.}",

note = "Publisher Copyright: {\textcopyright} 2019 by the American Diabetes Association.",

year = "2020",

month = jan,

day = "1",

doi = "10.2337/dc19-0524",

language = "English (US)",

volume = "43",

pages = "98--105",

journal = "Diabetes care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

number = "1",

}

TY - JOUR

T1 - Maternal gestational diabetes mellitus and newborn DNA Methylation

T2 - Findings from the pregnancy and childhood epigenetics consortium

AU - Howe, Caitlin G.

AU - Cox, Bianca

AU - Fore, Ruby

AU - Jungius, James

AU - Kvist, Tuomas

AU - Lent, Samantha

AU - Miles, Harriet E.

AU - Salas, Lucas A.

AU - Rifas-Shiman, Sheryl

AU - Starling, Anne P.

AU - Yousefi, Paul

AU - Ladd-Acosta, Christine

AU - Baccarelli, Andrea

AU - Binder, Elisabeth B.

AU - Chatzi, Vaia Lida

AU - Czamara, Darina

AU - Dabelea, Dana

AU - DeMeo, Dawn L.

AU - Ghantous, Akram

AU - Herceg, Zdenko

AU - Kajantie, Eero

AU - Lahti, Jari M.T.

AU - Lawlor, Debbie A.

AU - Litonjua, Augusto

AU - Nawrot, Tim S.

AU - Nohr, Ellen A.

AU - Oken, Emily

AU - Pizzi, Costanza

AU - Plusquin, Michelle

AU - Räikkönen, Katri

AU - Relton, Caroline L.

AU - Sharp, Gemma C.

AU - Sørensen, Thorkild I.A.

AU - Sunyer, Jordi

AU - Vrijheid, Martine

AU - Zhang, Weiming

AU - Hivert, Marie France

AU - Breton, Carrie V.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-Analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, usingDNAmethylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations betweenGDMandDNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-Analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene bodyof CYP2E1. IndividualCpGanalyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS MaternalGDMwas associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.

AB - OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-Analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, usingDNAmethylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations betweenGDMandDNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-Analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene bodyof CYP2E1. IndividualCpGanalyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS MaternalGDMwas associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.

UR - http://www.scopus.com/inward/record.url?scp=85077016621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077016621&partnerID=8YFLogxK

U2 - 10.2337/dc19-0524

DO - 10.2337/dc19-0524

M3 - Article

C2 - 31601636

AN - SCOPUS:85077016621

SN - 0149-5992

VL - 43

SP - 98

EP - 105

JO - Diabetes care

JF - Diabetes care

IS - 1

ER -

Maternal gestational diabetes mellitus and newborn DNA Methylation: Findings from the pregnancy and childhood epigenetics consortium

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this