Paternal DNA Methylation May Be Associated With Gestational Age at Birth.
Epigenetics
gestational age
paternal DNA methylation
Journal
Epigenetics insights
ISSN: 2516-8657
Titre abrégé: Epigenet Insights
Pays: United States
ID NLM: 101735398
Informations de publication
Date de publication:
2020
2020
Historique:
received:
20
04
2020
accepted:
09
05
2020
entrez:
23
9
2020
pubmed:
24
9
2020
medline:
24
9
2020
Statut:
epublish
Résumé
How epigenetic modifications of DNA are associated with gestational age at birth is not fully understood. We investigated potential effects of differential paternal DNA methylation (DNAm) on offspring gestational age at birth by conducting an epigenome-wide search for cytosine-phosphate-guanine (CpG) sites. Study participants in this study consist of male cohort members or partners of the F1-generation of the Isle of Wight Birth Cohort (IoWBC). DNAm levels in peripheral blood from F1-fathers (n = 92) collected around pregnancy of their spouses were analyzed using the Illumina 450K array. A 5-step statistical analysis was performed. First, a training-testing screening approach was applied to select CpG sites that are potentially associated with gestational age at birth. Second, functional enrichment analysis was employed to identify biological processes. Third, by centralizing on biologically informative genes, Cox proportional hazards models were used to assess the hazard ratios of individual paternal CpGs on gestational age adjusting for confounders. Fourth, to assess the validity of our results, we compared our CpG-gestational age correlations within a Born into Life Study in Sweden (n = 15). Finally, we investigated the correlation between the detected CpGs and differential gene expression in F2 cord blood in the IoWBC. Analysis of DNAm of fathers collected around their partner's pregnancy identified 216 CpG sites significantly associated with gestational age at birth. Functional enrichment pathways analyses of the annotated genes revealed 2 biological pathways significantly related to cell-cell membrane adhesion molecules. Differential methylation of 9 cell membrane adhesion pathway-related CpGs were significantly associated with gestational age at birth after adjustment for confounders. The replication sample showed correlation coefficients of 2 pathway-related CpGs with gestational age at birth within 95% confidence intervals of correlation coefficients in IoWBC. Finally, CpG sites of protocadherin ( Our findings suggest that differential paternal DNAm may affect gestational age at birth through cell-cell membrane adhesion molecules. The results are novel but require future replication in a larger cohort.
Sections du résumé
BACKGROUND
BACKGROUND
How epigenetic modifications of DNA are associated with gestational age at birth is not fully understood. We investigated potential effects of differential paternal DNA methylation (DNAm) on offspring gestational age at birth by conducting an epigenome-wide search for cytosine-phosphate-guanine (CpG) sites.
METHODS
METHODS
Study participants in this study consist of male cohort members or partners of the F1-generation of the Isle of Wight Birth Cohort (IoWBC). DNAm levels in peripheral blood from F1-fathers (n = 92) collected around pregnancy of their spouses were analyzed using the Illumina 450K array. A 5-step statistical analysis was performed. First, a training-testing screening approach was applied to select CpG sites that are potentially associated with gestational age at birth. Second, functional enrichment analysis was employed to identify biological processes. Third, by centralizing on biologically informative genes, Cox proportional hazards models were used to assess the hazard ratios of individual paternal CpGs on gestational age adjusting for confounders. Fourth, to assess the validity of our results, we compared our CpG-gestational age correlations within a Born into Life Study in Sweden (n = 15). Finally, we investigated the correlation between the detected CpGs and differential gene expression in F2 cord blood in the IoWBC.
RESULTS
RESULTS
Analysis of DNAm of fathers collected around their partner's pregnancy identified 216 CpG sites significantly associated with gestational age at birth. Functional enrichment pathways analyses of the annotated genes revealed 2 biological pathways significantly related to cell-cell membrane adhesion molecules. Differential methylation of 9 cell membrane adhesion pathway-related CpGs were significantly associated with gestational age at birth after adjustment for confounders. The replication sample showed correlation coefficients of 2 pathway-related CpGs with gestational age at birth within 95% confidence intervals of correlation coefficients in IoWBC. Finally, CpG sites of protocadherin (
CONCLUSIONS
CONCLUSIONS
Our findings suggest that differential paternal DNAm may affect gestational age at birth through cell-cell membrane adhesion molecules. The results are novel but require future replication in a larger cohort.
Identifiants
pubmed: 32964196
doi: 10.1177/2516865720930701
pii: 10.1177_2516865720930701
pmc: PMC7488897
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2516865720930701Subventions
Organisme : NIAID NIH HHS
ID : R01 AI091905
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132321
Pays : United States
Informations de copyright
© The Author(s) 2020.
Déclaration de conflit d'intérêts
Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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