Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude.

IF 5.7 2区 医学 Q1 Medicine
Latha Kadalayil, Md Zahangir Alam, Cory Haley White, Akram Ghantous, Esther Walton, Olena Gruzieva, Simon Kebede Merid, Ashish Kumar, Ritu P Roy, Olivia Solomon, Karen Huen, Brenda Eskenazi, Peter Rzehak, Veit Grote, Jean-Paul Langhendries, Elvira Verduci, Natalia Ferre, Darek Gruszfeld, Lu Gao, Weihua Guan, Xuehuo Zeng, Enrique F Schisterman, John F Dou, Kelly M Bakulski, Jason I Feinberg, Munawar Hussain Soomro, Giancarlo Pesce, Nour Baiz, Elena Isaevska, Michelle Plusquin, Marina Vafeiadi, Theano Roumeliotaki, Sabine A S Langie, Arnout Standaert, Catherine Allard, Patrice Perron, Luigi Bouchard, Evelien R van Meel, Janine F Felix, Vincent W V Jaddoe, Paul D Yousefi, Cecilia H Ramlau-Hansen, Caroline L Relton, Elmar W Tobi, Anne P Starling, Ivana V Yang, Maria Llambrich, Gillian Santorelli, Johanna Lepeule, Lucas A Salas, Mariona Bustamante, Susan L Ewart, Hongmei Zhang, Wilfried Karmaus, Stefan Röder, Ana Claudia Zenclussen, Jianping Jin, Wenche Nystad, Christian M Page, Maria Magnus, Dereje D Jima, Cathrine Hoyo, Rachel L Maguire, Tuomas Kvist, Darina Czamara, Katri Räikkönen, Tong Gong, Vilhelmina Ullemar, Sheryl L Rifas-Shiman, Emily Oken, Catarina Almqvist, Robert Karlsson, Jari Lahti, Susan K Murphy, Siri E Håberg, Stephanie London, Gunda Herberth, Hasan Arshad, Jordi Sunyer, Regina Grazuleviciene, Dana Dabelea, Régine P M Steegers-Theunissen, Ellen A Nohr, Thorkild I A Sørensen, Liesbeth Duijts, Marie-France Hivert, Vera Nelen, Maja Popovic, Manolis Kogevinas, Tim S Nawrot, Zdenko Herceg, Isabella Annesi-Maesano, M Daniele Fallin, Edwina Yeung, Carrie V Breton, Berthold Koletzko, Nina Holland, Joseph L Wiemels, Erik Melén, Gemma C Sharp, Matt J Silver, Faisal I Rezwan, John W Holloway
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Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear.</p><p><strong>Methods: </strong>We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points.</p><p><strong>Results: </strong>We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. 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DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N).</p><p><strong>Conclusions: </strong>In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). 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引用次数: 0

Abstract

Background: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear.

Methods: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points.

Results: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N).

Conclusions: In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes.

Abstract Image

Abstract Image

Abstract Image

对出生时和儿童期DNA甲基化的分析揭示了与出生季节和纬度相关的变化。
背景:出生或妊娠期间环境暴露的季节性变化与许多成年特征和日后的健康结果有关。DNA甲基化(DNAm)是否在出生季节和终身表型之间的分子机制中发挥作用尚不清楚。方法:我们在妊娠和儿童表观遗传学联盟中进行了表观基因组范围的荟萃分析,以确定DNAm与出生季节的相关性,包括差异甲基化探针(DMPs)和区域(DMRs)。在两个时间点检查了相关性:出生时(21个队列,N = 9358)和1-11岁的儿童(12个队列,N = 3610)。我们进行了荟萃分析,以评估纬度对两个时间点出生季节特定关联的影响。结果:我们确定了出生季节和DNAm之间的相关性(错误发现率调整p值 结论:在这项大规模的表观基因组荟萃分析研究中,我们为(i)DNAm和出生季节之间的关联提供了证据,这种关联在一年中的季节中是独特的(时间效应),以及(ii)季节关联的纬度依赖性变化(空间效应)。DNAm可能在出生季节对成人健康结果影响的分子机制中发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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