Dataset Information

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

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.

SUBMITTER: Solomon O

PROVIDER: S-EPMC9623595 | biostudies-literature | 2022 Jan-Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

Solomon Olivia O Huen Karen K Yousefi Paul P Küpers Leanne K LK González Juan R JR Suderman Matthew M Reese Sarah E SE Page Christian M CM Gruzieva Olena O Rzehak Peter P Gao Lu L Bakulski Kelly M KM Novoloaca Alexei A Allard Catherine C Pappa Irene I Llambrich Maria M Vives Marta M Jima Dereje D DD Kvist Tuomas T Baccarelli Andrea A White Cory C Rezwan Faisal I FI Sharp Gemma C GC Tindula Gwen G Bergström Anna A Grote Veit V Dou John F JF Isaevska Elena E Magnus Maria C MC Corpeleijn Eva E Perron Patrice P Jaddoe Vincent W V VWV Nohr Ellen A EA Maitre Lea L Foraster Maria M Hoyo Cathrine C Håberg Siri E SE Lahti Jari J DeMeo Dawn L DL Zhang Hongmei H Karmaus Wilfried W Kull Inger I Koletzko Berthold B Feinberg Jason I JI Gagliardi Luigi L Bouchard Luigi L Ramlau-Hansen Cecilia Høst CH Tiemeier Henning H Santorelli Gillian G Maguire Rachel L RL Czamara Darina D Litonjua Augusto A AA Langhendries Jean-Paul JP Plusquin Michelle M Lepeule Johanna J Binder Elisabeth B EB Verduci Elvira E Dwyer Terence T Carracedo Ángel Á Ferre Natalia N Eskenazi Brenda B Kogevinas Manolis M Nawrot Tim S TS Munthe-Kaas Monica C MC Herceg Zdenko Z Relton Caroline C Melén Erik E Gruszfeld Dariusz D Breton Carrie C Fallin M D MD Ghantous Akram A Nystad Wenche W Heude Barbara B Snieder Harold H Hivert Marie-France MF Felix Janine F JF Sørensen Thorkild I A TIA Bustamante Mariona M Murphy Susan K SK Raikkönen Katri K Oken Emily E Holloway John W JW Arshad Syed Hasan SH London Stephanie J SJ Holland Nina N

Mutation research. Reviews in mutation research 20220101

<h4>Background</h4>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.<h4>Methods</h4>We performed a meta-analysis of the association of sex and cord blood D ...[more]

PMID: 35690418

Similar Datasets

Project description:BackgroundPrenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes.ObjectivesWe aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children.MethodsWe meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression.ResultsSix CpGs were significantly associated [false discovery rate (FDR) [Formula: see text]] with prenatal [Formula: see text] and 14 with [Formula: see text] exposure. Two of the [Formula: see text] CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant ([Formula: see text]) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent [Formula: see text] exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal [Formula: see text] and or [Formula: see text] exposure, of which two [Formula: see text] DMRs, including H19 and MARCH11, replicated in newborns.ConclusionsSeveral differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. https://doi.org/10.1289/EHP4522.

Dataset Information

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

Background

Methods

Results

Conclusions

Publications

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets