Author, as appears in the article.: Solomon O; Huen K; Yousefi P; Küpers LK; González JR; Suderman M; Reese SE; Page CM; Gruzieva O; Rzehak P; Gao L; Bakulski KM; Novoloaca A; Allard C; Pappa I; Llambrich M; Vives M; Jima DD; Kvist T; Baccarelli A; White C; Rezwan FI; Sharp GC; Tindula G; Bergström A; Grote V; Dou JF; Isaevska E; Magnus MC; Corpeleijn E; Perron P; Jaddoe VWV; Nohr EA; Maitre L; Foraster M; Hoyo C; Håberg SE; Lahti J; DeMeo DL; Zhang H; Karmaus W; Kull I; Koletzko B; Feinberg JI; Gagliardi L; Bouchard L; Ramlau-Hansen CH; Tiemeier H; Santorelli G; Maguire RL; Czamara D; Litonjua AA; Langhendries JP; Plusquin M; Lepeule J; Binder EB; Verduci E; Dwyer T; Carracedo Á; Ferre N; Eskenazi B; Kogevinas M; Nawrot TS; Munthe-Kaas MC; Herceg Z; Relton C; Melén E; Gruszfeld D; Breton C; Fallin MD; Ghantous A; Nystad W; Heude B; Snieder H; Hivert MF; Felix JF; Sørensen TIA; Bustamante M; Murphy SK; Raikkönen K; Oken E; Holloway JW; Arshad SH; London SJ; Holland N

Department: Medicina i Cirurgia

URV's Author/s: Ferre Pallas, Natalia

Keywords: Sex Gene Ewas Dna methylation Cord blood Children sex pregnancy package information gender expression ewas cord blood children

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.

Thematic Areas: Toxicology Medicina ii Medicina i Health, toxicology and mutagenesis Genetics & heredity Genetics General medicine Farmacia Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología Biotechnology & applied microbiology Biodiversidade

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: natalia.ferre@urv.cat

Author identifier: 0000-0002-2838-1525

Record's date: 2023-02-19

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.sciencedirect.com/science/article/pii/S1383574222000059

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Mutation Research-Reviews In Mutation Research. 789

APA: Solomon O; Huen K; Yousefi P; Küpers LK; González JR; Suderman M; Reese SE; Page CM; Gruzieva O; Rzehak P; Gao L; Bakulski KM; Novoloaca A; Allard C; (2022). Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation. Mutation Research-Reviews In Mutation Research, 789(), -. DOI: 10.1016/j.mrrev.2022.108415

Article's DOI: 10.1016/j.mrrev.2022.108415

Entity: Universitat Rovira i Virgili

Journal publication year: 2022

Publication Type: Journal Publications