新生儿和儿童表观基因组关联研究的元分析表明，在血液DNA甲基化方面普遍存在性别差异。
Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.
发表日期：2022
作者：
Olivia Solomon, Karen Huen, Paul Yousefi, Leanne K Küpers, Juan R González, Matthew Suderman, Sarah E Reese, Christian M Page, Olena Gruzieva, Peter Rzehak, Lu Gao, Kelly M Bakulski, Alexei Novoloaca, Catherine Allard, Irene Pappa, Maria Llambrich, Marta Vives, Dereje D Jima, Tuomas Kvist, Andrea Baccarelli, Cory White, Faisal I Rezwan, Gemma C Sharp, Gwen Tindula, Anna Bergström, Veit Grote, John F Dou, Elena Isaevska, Maria C Magnus, Eva Corpeleijn, Patrice Perron, Vincent W V Jaddoe, Ellen A Nohr, Lea Maitre, Maria Foraster, Cathrine Hoyo, Siri E Håberg, Jari Lahti, Dawn L DeMeo, Hongmei Zhang, Wilfried Karmaus, Inger Kull, Berthold Koletzko, Jason I Feinberg, Luigi Gagliardi, Luigi Bouchard, Cecilia Høst Ramlau-Hansen, Henning Tiemeier, Gillian Santorelli, Rachel L Maguire, Darina Czamara, Augusto A Litonjua, Jean-Paul Langhendries, Michelle Plusquin, Johanna Lepeule, Elisabeth B Binder, Elvira Verduci, Terence Dwyer, Ángel Carracedo, Natalia Ferre, Brenda Eskenazi, Manolis Kogevinas, Tim S Nawrot, Monica C Munthe-Kaas, Zdenko Herceg, Caroline Relton, Erik Melén, Dariusz Gruszfeld, Carrie Breton, M D Fallin, Akram Ghantous, Wenche Nystad, Barbara Heude, Harold Snieder, Marie-France Hivert, Janine F Felix, Thorkild I A Sørensen, Mariona Bustamante, Susan K Murphy, Katri Raikkönen, Emily Oken, John W Holloway, Syed Hasan Arshad, Stephanie J London, Nina Holland
来源：
Mutat Res-Rev Mutat
摘要：
在儿童中观察到了性别特异性差异，包括哮喘、免疫反应、代谢健康、一些儿童和成人癌症以及精神障碍等健康状况的发病率、发病年龄和易感性。表观遗传修饰如DNA甲基化可能在这些性别差异中发挥作用。我们对来自参加妊娠和儿童表观遗传学联合组(PACE)的17个队列的8438个新生儿中的450,000个以上CpG位点的性别和脐带血DNA甲基化进行了元分析。我们还从8个队列(n=4268)中检查了5.5-10岁的较大儿童的DNA甲基化和儿童性别的关联。在新生儿的血液中，经过白细胞比例和批次的调整后，性别与46,979个性染色体CpG位点的DNA甲基化差异(P<1.3×10-7)显著相关。其中大多数位点男性的DNA甲基化水平低于女性。在新生儿血液中鉴定的不同甲基化CpG位点中，68%(31,727)在较大儿童中达到了查找水平的显著性(p<1.1×10-6)，并且具有相同方向的DNA甲基化差异。这是一项关于新生儿和较大儿童DNA甲基化性别差异的大规模元分析。扩展之前的研究，我们复制了先前的发现，并发现了更多具有性别特异性差异的染色体位点的DNA甲基化。不同甲基化位点富集在癌症、精神障碍和心血管表型相关基因中。版权所有 © 2022作者。由Elsevier B.V.出版。保留所有权利。
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.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).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.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.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.