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Title: | Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation | Authors: | Solomon, Olivia Huen, Karen Yousefi, Paul Kupers, Leanne K. Gonzalez, Juan R. Suderman, Matthew Reese, Sarah E. Page, Christian M. Gruzieva, Olena Rzehak, Peter Gao, Lu Bakulski, Kelly M. Novoloaca, Alexei Allard, Catherine Pappa, Irene Llambrich, Maria Vives, Marta Jima, Dereje D. Kvist, Tuomas Baccarelli, Andrea White, Cory Rezwan, Faisal, I Sharp, Gemma C. Tindula, Gwen Bergstrom, Anna Grote, Veit Dou, John F. Isaevska, Elena Magnus, Maria C. Corpeleijn, Eva Perron, Patrice Jaddoe, Vincent W. V. Nohr, Ellen A. Maitre, Lea Foraster, Maria Hoyo, Cathrine Haberg, Siri E. Lahti, Jari DeMeo, Dawn L. Zhang , Hongmei Karmaus, Wilfried Kull, Inger Koletzko, Berthold Feinberg, Jason, I Gagliardi, Luigi Bouchard, Luigi Ramlau-Hansen, Cecilia Host Tiemeier, Henning Santorelli, Gillian Maguire, Rachel L. Czamara, Darina Litonjua, Augusto A. Langhendries, Jean-Paul PLUSQUIN, Michelle Lepeule, Johanna Binder, Elisabeth B. Verduci, Elvira Dwyer, Terence Carracedo, Angel Ferre, Natalia Eskenazi, Brenda Kogevinas, Manolis NAWROT, Tim Munthe-Kaas, Monica C. Herceg, Zdenko Relton, Caroline Melen, Erik Gruszfeld, Dariusz Breton, Carrie Fallin, M. D. Ghantous, Akram Nystad, Wenche Heude, Barbara Snieder, Harold Hivert, Marie-France Felix, Janine F. Sorensen, Thorkild I. A. Bustamante, Mariona Murphy, Susan K. Raikkonen, Katri Oken, Emily Holloway, John W. Arshad, Syed Hasan London, Stephanie J. Holland , Nina |
Issue Date: | 2022 | Publisher: | ELSEVIER | Source: | Mutation research. Reviews in mutation research (Print), 789 (Art N° 108415) | 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.& nbsp;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).& nbsp;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 x 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 x 10-6) in older children and had methylation differences in the same direction.& nbsp;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. | Notes: | Huen, K (corresponding author), Univ Calif Berkeley, Sch Publ Hlth, 2121 Berkeley Way, Berkeley, CA 94720 USA. khuen@berkeley.edu |
Keywords: | DNA methylation;Sex;Children;Cord blood;EWAS | Document URI: | http://hdl.handle.net/1942/37610 | ISSN: | 1383-5742 | e-ISSN: | 1388-2139 | DOI: | 10.1016/j.mrrev.2022.108415 | ISI #: | WOS:000801882100002 | 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/bync-nd/4.0/). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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