Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation
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- dc.contributor.author Solomon, Olivia
- dc.contributor.author González, Juan Ramón
- dc.contributor.author Llambrich, Maria
- dc.contributor.author Vives Usano, Marta, 1990-
- dc.contributor.author Maitre, Léa
- dc.contributor.author Foraster Pulido, Maria, 1984-
- dc.contributor.author Kogevinas, Manolis
- dc.contributor.author Bustamante Pineda, Mariona
- dc.contributor.author Holland, Nina
- dc.date.accessioned 2022-11-04T07:45:35Z
- dc.date.available 2022-11-04T07:45:35Z
- dc.date.issued 2022
- dc.description.abstract Background: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268). Results: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction. Conclusions: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.
- dc.format.mimetype application/pdf
- dc.identifier.citation Solomon O, Huen K, Yousefi P, Küpers LK, González JR, Suderman M et al. Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation. Mutat Res Rev Mutat Res. 2022 Jan-Jun;789:108415. DOI: 10.1016/j.mrrev.2022.108415
- dc.identifier.doi http://dx.doi.org/10.1016/j.mrrev.2022.108415
- dc.identifier.issn 1383-5742
- dc.identifier.uri http://hdl.handle.net/10230/54691
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Mutat Res Rev Mutat Res. 2022 Jan-Jun;789:108415
- dc.rights © 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword Children
- dc.subject.keyword Cord blood
- dc.subject.keyword DNA methylation
- dc.subject.keyword EWAS
- dc.subject.keyword Sex
- dc.title Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion