Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence
Priyanka Choudhary, Giulietta S. Monasso, Ville Karhunen, Justiina Ronkainen, Giulia Mancano, Caitlin G. Howe, Zhongzheng Niu, Xuehuo Zeng, Weihua Guan, John Dou, Jason I. Feinberg, Charles E. Mordaunt, Giancarlo Pesce, Nour Baïz, Rossella Alfano, Dries S. Martens, Congrong Wang, Elena Isaevska, Elina Keikkala, Sanna Mustaniemi, Chris H. L. Thio, Eliza Fraszczyk, Elmar W. Tobi, Anne P. Starling, Marta Cosín‐Tomás, José Urquiza, Stefan Röder, Thanh T. Hoang, Christian M. Page, Dereje D. Jima, John S. House, Rachel L. Maguire, Raffael Ott, Xenia Pawlow, Lea Sirignano, Lea Zillich, Anni Malmberg, Sebastian Rauschert, Phillip E. Melton, Tong Gong, Robert Karlsson, Ruby Fore, Wei Perng, Zachary M. Laubach, Darina Czamara, Gemma C. Sharp, Carrie V. Breton, Enrique F. Schisterman, Edwina Yeung, Sunni L. Mumford, M. Daniele Fallin, Janine M. LaSalle, Rebecca J. Schmidt, Kelly M. Bakulski, Isabella Annesi‐Maesano, Barbara Heude, Tim S. Nawrot, Michelle Plusquin, Akram Ghantous, Zdenko Herceg, Lorenza Nisticò, Marina Vafeiadi, Manolis Kogevinas, Marja Vääräsmäki, Eero Kajantie, Harold Snieder, Eva Corpeleijn, Régine P.M. Steegers‐Theunissen, Ivana V. Yang, Dana Dabelea, Serena Fossati, Ana Claudia Zenclussen, Gunda Herberth, Maria C. Magnus, Siri E. Håberg, Stephanie J. London, Monica Cheng Munthe‐Kaas, Susan K. Murphy, Cathrine Hoyo, Anette‐G. Ziegler, Sandra Hummel, Stephanie H. Witt, Fabian Streit, Josef Frank, Katri Räikkönen, Jari Lahti, Rae‐Chi Huang, Catarina Almqvist, Marie‐France Hivert, Vincent W. V. Jaddoe, Marjo‐Riitta Järvelin, Marko Kantomaa, Janine F. Felix, Sylvain Sebért
Abstract
Abstract Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth ( n = 9 881), in childhood ( n = 2 017), and adolescence ( n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B 12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.