Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence
Authors: Choudhary Priyanka , Monasso Giulietta S. , Karhunen Ville , Ronkainen Justiina , Mancano Giulia , Howe Caitlin G. , Niu Zhongzheng , Zeng Xuehuo , Guan Weihua , Dou John , Feinberg Jason I. , Mordaunt Charles , Pesce Giancarlo , Baïz Nour , Alfano Rossella , Martens Dries S. , Wang Congrong , Isaevska Elena , Keikkala Elina , Mustaniemi Sanna , Thio Chris H. L. , Fraszczyk Eliza , Tobi Elmar W. , Starling Anne P. , Cosin-Tomas Marta , Urquiza Jose , Röder Stefan , Hoang Thanh T. , Page Christian , Jima Dereje D. , House John S. , Maguire Rachel L. , Ott Raffael , Pawlow Xenia , Sirignano Lea , Zillich Lea , Malmberg Anni , Rauschert Sebastian , Melton Phillip , Gong Tong , Karlsson Robert , Fore Ruby , Perng Wei , Laubach Zachary M. , Czamara Darina , Sharp Gemma , Breton Carrie V. , Schisterman Enrique , Yeung Edwina , Mumford Sunni L. , Fallin M. Daniele , LaSalle Janine M. , Schmidt Rebecca J. , Bakulski Kelly M. , Annesi-Maesano Isabella , Heude Barbara , Nawrot Tim S. , Plusquin Michelle , Ghantous Akram , Herceg Zdenko , Nisticò Lorenza , Vafeiadi Marina , Kogevinas Manolis , Vääräsmäki Marja , Kajantie Eero , Snieder Harold , Corpeleijn Eva , Steegers-Theunissen Regine P. M. , Yang Ivana V. , Dabelea Dana , Fossati Serena , Zenclussen Ana C. , Herberth Gunda , Magnus Maria , Håberg Siri E. , London Stephanie J. , Munthe-Kaas Monica Cheng , Murphy Susan K. , Hoyo Cathrine , Ziegler Anette-G , Hummel Sandra , Witt Stephanie H. , Streit Fabian , Frank Josef , Räikkönen Katri , Lahti Jari , Huang Rae-chi , Almqvist Catarina , Hivert Marie-France , Jaddoe Vincent W. V. , Järvelin Marjo-Riitta , Kantomaa Marko , Felix Janine F. , Sebert Sylvain 
Published: December 2023

AbstractMaternal 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-B12 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.