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Association of maternal DNA methylation and offspring birthweight

Association of maternal DNA methylation and offspring birthweight
Association of maternal DNA methylation and offspring birthweight
This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight.One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentiallymethylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral bloodsamples were drawn from mothers at 22–38 weeks of pregnancy for epigenome-wide DNAm assessment using the IlluminaInfinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training andtesting process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80%of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs.The Swedish Born Into Life cohort was used to replicate our findings (n= 33). Eight candidate CpGs corresponding to the genesLMF1,KIF9,KLHL18,DAB1,VAX2,CD207,SCT,SCYL2,DEPDC4,NECAP1,andSFRS3in mothers were identified asstatistically significantly associated with their children’s birthweight in the IOW cohort and confirmed by linear mixed modelsafter adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 withpvalues = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1,VAX2,CD207,andNECAP1)weremargin-ally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possiblysustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (in-volved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternalinvolvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic toolrecognizing mothers at risk for pregnancies ending with altered birthweights
Birthweight, DNA methylation, Epigenetics, Epigenome-Wide Association Study, Pregnancy
1933-7191
218-227
Rahimabad, Parnian Kheirkhah
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Arshad, Syed
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Holloway, John
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Mukherjee, Nadini
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Hedman, Anna M.
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Gruzieva, Olena
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Andolf, Ellika
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Kere, Juha
57c301de-f111-4552-a585-13eed945bdfc
Pershagen, Göran
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Almqvist, Catarina
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Jiang, Yu
4fa0a27b-8c06-4988-832a-8f5fb3a3f1ec
Chen, Su
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Karmaus, Wilfried
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Rahimabad, Parnian Kheirkhah
2afee050-98f5-433f-b353-73ce7b5087ed
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Mukherjee, Nadini
3ffe22a5-0d03-49b2-a7b5-1131c1a447ce
Hedman, Anna M.
1a78c62e-8caf-4b18-b275-3a991a5e41f6
Gruzieva, Olena
0865d16b-2fdc-4e58-b834-a9fd22283ca5
Andolf, Ellika
218974e3-872a-4ee9-9ff0-4721d1dc09a8
Kere, Juha
57c301de-f111-4552-a585-13eed945bdfc
Pershagen, Göran
5680dad3-cd15-4752-a61a-49f3502953ef
Almqvist, Catarina
68bd5bec-1e94-4252-96b8-485c8308561c
Jiang, Yu
4fa0a27b-8c06-4988-832a-8f5fb3a3f1ec
Chen, Su
66e5d980-713f-46c5-9264-38c3600c77ab
Karmaus, Wilfried
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Rahimabad, Parnian Kheirkhah, Arshad, Syed, Holloway, John, Mukherjee, Nadini, Hedman, Anna M., Gruzieva, Olena, Andolf, Ellika, Kere, Juha, Pershagen, Göran, Almqvist, Catarina, Jiang, Yu, Chen, Su and Karmaus, Wilfried (2021) Association of maternal DNA methylation and offspring birthweight. Reproductive Sciences, 28 (1), 218-227. (doi:10.1007/s43032-020-00281-9).

Record type: Article

Abstract

This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight.One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentiallymethylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral bloodsamples were drawn from mothers at 22–38 weeks of pregnancy for epigenome-wide DNAm assessment using the IlluminaInfinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training andtesting process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80%of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs.The Swedish Born Into Life cohort was used to replicate our findings (n= 33). Eight candidate CpGs corresponding to the genesLMF1,KIF9,KLHL18,DAB1,VAX2,CD207,SCT,SCYL2,DEPDC4,NECAP1,andSFRS3in mothers were identified asstatistically significantly associated with their children’s birthweight in the IOW cohort and confirmed by linear mixed modelsafter adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 withpvalues = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1,VAX2,CD207,andNECAP1)weremargin-ally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possiblysustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (in-volved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternalinvolvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic toolrecognizing mothers at risk for pregnancies ending with altered birthweights

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Accepted/In Press date: 27 July 2020
e-pub ahead of print date: 4 August 2020
Published date: 1 January 2021
Keywords: Birthweight, DNA methylation, Epigenetics, Epigenome-Wide Association Study, Pregnancy

Identifiers

Local EPrints ID: 443213
URI: http://eprints.soton.ac.uk/id/eprint/443213
ISSN: 1933-7191
PURE UUID: 61b7ac33-0a5c-4718-a9e2-b7496b1f37aa
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 17 Aug 2020 16:30
Last modified: 26 Nov 2021 02:40

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Contributors

Author: Parnian Kheirkhah Rahimabad
Author: Syed Arshad
Author: John Holloway ORCID iD
Author: Nadini Mukherjee
Author: Anna M. Hedman
Author: Olena Gruzieva
Author: Ellika Andolf
Author: Juha Kere
Author: Göran Pershagen
Author: Catarina Almqvist
Author: Yu Jiang
Author: Su Chen
Author: Wilfried Karmaus

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