Association of Maternal DNA Methylation and Offspring Birthweight.
Birthweight
DNA methylation
Epigenetics
Epigenome-Wide Association Study
Pregnancy
Journal
Reproductive sciences (Thousand Oaks, Calif.)
ISSN: 1933-7205
Titre abrégé: Reprod Sci
Pays: United States
ID NLM: 101291249
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
10
05
2020
accepted:
27
07
2020
pubmed:
6
8
2020
medline:
24
11
2021
entrez:
6
8
2020
Statut:
ppublish
Résumé
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 differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing 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 genes LMF1, KIF9, KLHL18, DAB1, VAX2, CD207, SCT, SCYL2, DEPDC4, NECAP1, and SFRS3 in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 with p values = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1, VAX2, CD207, and NECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.
Identifiants
pubmed: 32754889
doi: 10.1007/s43032-020-00281-9
pii: 10.1007/s43032-020-00281-9
pmc: PMC7785565
mid: NIHMS1617888
doi:
Substances chimiques
DNA
9007-49-2
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
218-227Subventions
Organisme : NIAID NIH HHS
ID : R01 AI091905
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL082925
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132321
Pays : United States
Références
Bioessays. 2013 Jan;35(1):34-45
pubmed: 23147242
Placenta. 2010 Oct;31(10):839-47
pubmed: 20716463
Front Endocrinol (Lausanne). 2019 Mar 20;10:160
pubmed: 30949130
Endocrine. 2002 Oct;19(1):43-55
pubmed: 12583601
Annu Rev Immunol. 2004;22:33-54
pubmed: 15032573
Obstet Gynecol Sci. 2017 Nov;60(6):506-519
pubmed: 29184858
Eur J Obstet Gynecol Reprod Biol. 2013 Nov;171(1):3-8
pubmed: 23932305
Genet Epigenet. 2017 Jul 28;9:1179237X17721540
pubmed: 28811741
Sci Immunol. 2019 Jan 11;4(31):
pubmed: 30635356
J Cancer. 2019 Jun 9;10(15):3459-3471
pubmed: 31293650
BMC Bioinformatics. 2012 May 08;13:86
pubmed: 22568884
Epigenetics. 2017 Aug;12(8):616-625
pubmed: 28486003
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
BMC Pediatr. 2014 Oct 23;14:275
pubmed: 25339063
Immunity. 2000 Jan;12(1):71-81
pubmed: 10661407
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
Nestle Nutr Inst Workshop Ser. 2013;74:1-10
pubmed: 23887099
Horm Metab Res. 2014 Dec;46(13):911-20
pubmed: 25473824
Biomed Res Int. 2016;2016:2615348
pubmed: 27034928
Sheng Li Xue Bao. 2016 Dec 25;68(6):725-732
pubmed: 28004066
Reprod Sci. 2014 Jun;21(6):724-32
pubmed: 24336673
Ann N Y Acad Sci. 2006 Jul;1070:561-5
pubmed: 16888225
Int J Epidemiol. 2018 Aug 1;47(4):1043-1044i
pubmed: 29547889
Placenta. 2017 Sep;57:144-151
pubmed: 28864004
Nucleic Acids Res. 1988 Feb 11;16(3):1215
pubmed: 3344216
Placenta. 2018 Apr;64:53-60
pubmed: 29626981
Curr Pharm Biotechnol. 2014;15(1):24-31
pubmed: 24720597
Am J Reprod Immunol. 2017 May;77(5):
pubmed: 28194822
J Assist Reprod Genet. 2015 Mar;32(3):337-46
pubmed: 25533332
Placenta. 2011 Nov;32(11):811-6
pubmed: 21944867
BMC Bioinformatics. 2016 Aug 02;17:299
pubmed: 27480116
J Mol Biol. 2011 Jan 28;405(4):1027-39
pubmed: 21112338
Biol Reprod. 2007 Oct;77(4):590-8
pubmed: 17596562
Nat Commun. 2019 Apr 23;10(1):1893
pubmed: 31015461
Nucleic Acids Res. 2018 Jan 4;46(D1):D762-D769
pubmed: 29106570
BMC Bioinformatics. 2010 Nov 30;11:587
pubmed: 21118553
J Biol Chem. 2013 Dec 27;288(52):36762-71
pubmed: 24217250
Nutr Metab (Lond). 2014 Aug 16;11:37
pubmed: 25302068
Arch Dis Child. 2006 Apr;91(4):334-9
pubmed: 16428358
Bioinformatics. 2012 Mar 1;28(5):729-30
pubmed: 22253290
BMC Res Notes. 2018 Jul 9;11(1):447
pubmed: 29986740
Biochim Biophys Acta. 2012 May;1821(5):790-4
pubmed: 22063272
Acta Paediatr. 2018 Jun;107(6):1003-1010
pubmed: 29385276
Methods Mol Biol. 2009;507:149-63
pubmed: 18987813
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11
pubmed: 19465376
Thorax. 2009 Jan;64(1):62-6
pubmed: 19001004