Maternal SARS-CoV-2 exposure alters infant DNA methylation.
DNA methylation
In utero
Maternal
Neurodevelopment
SARS-CoV-2
Journal
Brain, behavior, & immunity - health
ISSN: 2666-3546
Titre abrégé: Brain Behav Immun Health
Pays: United States
ID NLM: 101759062
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
21
08
2022
revised:
07
12
2022
accepted:
16
12
2022
entrez:
26
12
2022
pubmed:
27
12
2022
medline:
27
12
2022
Statut:
ppublish
Résumé
Infection during pregnancy can increase the risk of neurodevelopmental disorders in offspring. The impact of maternal SARS-CoV-2 infection on infant neurodevelopment is poorly understood. The maternal immune response to infection may be mimicked in rodent models of maternal immune activation which recapitulate altered neurodevelopment and behavioural disturbances in the offspring. In these models, epigenetic mechanisms, in particular DNA methylation, are one pathway through which this risk is conferred DNA was extracted from buccal swab specimens from (n = 4) SARS-CoV-2 1962 hypermethylated CpG sites were identified with an unadjusted p-value of 0.05, where 1133 CpGs mapped to 959 unique protein coding genes, and 716 hypomethylated CpG sites mapped to 559 unique protein coding genes in SARS-CoV-2 exposed infants compared to non-exposed. One differentially methylated position (cg06758191), located in the gene body of AFAP1 that was hypomethylated in the SARS-CoV-2 exposed cohort was significant after correction for multiple testing (FDR-adjusted p-value <0.00083). Two significant differentially methylated regions were identified; a hypomethylated intergenic region located in chromosome 6p proximal to the genes ZP57 and HLA-F (fwer <0.004), and a hypomethylated region in the promoter and body of the gene GAREM2 (fwer <0.036). Gene network enrichment analysis revealed differential methylation in genes corresponding to pathways relevant to neurodevelopment, including the ERBB pathway. These pilot data suggest that exposure to SARS-CoV-2
Sections du résumé
Background
UNASSIGNED
Infection during pregnancy can increase the risk of neurodevelopmental disorders in offspring. The impact of maternal SARS-CoV-2 infection on infant neurodevelopment is poorly understood. The maternal immune response to infection may be mimicked in rodent models of maternal immune activation which recapitulate altered neurodevelopment and behavioural disturbances in the offspring. In these models, epigenetic mechanisms, in particular DNA methylation, are one pathway through which this risk is conferred
Methods
UNASSIGNED
DNA was extracted from buccal swab specimens from (n = 4) SARS-CoV-2
Results
UNASSIGNED
1962 hypermethylated CpG sites were identified with an unadjusted p-value of 0.05, where 1133 CpGs mapped to 959 unique protein coding genes, and 716 hypomethylated CpG sites mapped to 559 unique protein coding genes in SARS-CoV-2 exposed infants compared to non-exposed. One differentially methylated position (cg06758191), located in the gene body of AFAP1 that was hypomethylated in the SARS-CoV-2 exposed cohort was significant after correction for multiple testing (FDR-adjusted p-value <0.00083). Two significant differentially methylated regions were identified; a hypomethylated intergenic region located in chromosome 6p proximal to the genes ZP57 and HLA-F (fwer <0.004), and a hypomethylated region in the promoter and body of the gene GAREM2 (fwer <0.036). Gene network enrichment analysis revealed differential methylation in genes corresponding to pathways relevant to neurodevelopment, including the ERBB pathway.
Conclusion
UNASSIGNED
These pilot data suggest that exposure to SARS-CoV-2
Identifiants
pubmed: 36570792
doi: 10.1016/j.bbih.2022.100572
pii: S2666-3546(22)00162-4
pmc: PMC9758784
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100572Informations de copyright
© 2022 Published by Elsevier Inc.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Bioinformatics. 2004 Dec 12;20(18):3705-6
pubmed: 15297296
Diabetes Care. 2020 Jan;43(1):98-105
pubmed: 31601636
Transl Psychiatry. 2019 Jan 31;9(1):47
pubmed: 30705257
Mol Psychiatry. 2002;7(7):673-82
pubmed: 12192610
Int J Obes (Lond). 2019 Jun;43(6):1244-1255
pubmed: 30464231
JAMA Netw Open. 2022 Jun 1;5(6):e2215787
pubmed: 35679048
Bioinformatics. 2013 Jan 15;29(2):189-96
pubmed: 23175756
Mol Psychiatry. 2011 Mar;16(3):286-92
pubmed: 20157312
Innovation (Camb). 2021 Jul 01;2(3):100141
pubmed: 34557778
Genet Mol Biol. 2014 Jun;37(2):439-43
pubmed: 25071410
Zhonghua Gan Zang Bing Za Zhi. 2009 Mar;17(3):198-202
pubmed: 19335983
Biol Psychiatry. 2017 Feb 1;81(3):265-276
pubmed: 27769567
BMC Med Genomics. 2020 Jan 8;13(1):6
pubmed: 31914996
Neurosci Biobehav Rev. 2005;29(6):913-47
pubmed: 15964075
Mech Dev. 2015 Nov;138 Pt 1:8-16
pubmed: 26215350
Epigenetics Chromatin. 2015 Jan 27;8:6
pubmed: 25972926
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Arch Pediatr Adolesc Med. 2010 May;164(5):470-7
pubmed: 20439799
J Neurochem. 2017 Apr;141(2):247-262
pubmed: 28112407
Mol Psychiatry. 2021 Nov;26(11):6868-6879
pubmed: 33990769
J Clin Invest. 2020 Sep 1;130(9):4947-4953
pubmed: 32573498
Eur J Immunol. 2017 Jan;47(1):168-179
pubmed: 27861791
Mov Disord. 2014 Nov;29(13):1606-14
pubmed: 24375821
Arch Gen Psychiatry. 1988 Feb;45(2):189-92
pubmed: 3337616
Exp Cell Res. 2000 Feb 25;255(1):102-13
pubmed: 10666339
Hum Mol Genet. 2011 Jan 15;20(2):387-91
pubmed: 21037240
Epigenomics. 2009 Dec;1(2):239-59
pubmed: 20495664
Lancet Diabetes Endocrinol. 2017 Jan;5(1):53-64
pubmed: 27743978
J Cell Physiol. 2007 Dec;213(3):740-9
pubmed: 17520695
Bioinformatics. 2014 Feb 01;30(3):428-30
pubmed: 24336642
Annu Rev Med. 2019 Jan 27;70:151-166
pubmed: 30691368
Brain Behav Immun. 2022 Feb;100:70-82
pubmed: 34808289
J Biol Chem. 2013 Oct 11;288(41):29934-42
pubmed: 24003223
Elife. 2021 Feb 26;10:
pubmed: 33646943
Epigenetics. 2015;10(12):1143-55
pubmed: 26575259
Br J Psychiatry. 1987 Jun;150:782-6
pubmed: 3651732
Arch Gen Psychiatry. 2004 Aug;61(8):774-80
pubmed: 15289276
Dev Neurobiol. 2012 Oct;72(10):1272-6
pubmed: 22488761
Stat Appl Genet Mol Biol. 2004;3:Article3
pubmed: 16646809
Nucleus (Calcutta). 2021;64(3):259-270
pubmed: 34421129
Int J Epidemiol. 2012 Feb;41(1):200-9
pubmed: 22422453
Mol Neurobiol. 2020 Sep;57(9):3712-3726
pubmed: 32564287
Transl Psychiatry. 2014 Sep 02;4:e434
pubmed: 25180573
Epigenomics. 2015 Oct;7(7):1137-53
pubmed: 26067621