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 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 Cosin-Tomas,Jose Urquiza, Stefan Röder,Thanh T Hoang,Christian Page,Dereje D Jima,John S House,Rachel L Maguire,Raffael Ott, Xenia Pawlow,Lea Sirignano,Lea Zillich,Anni Malmberg,Sebastian Rauschert,Phillip Melton,Tong Gong,Robert Karlsson,Ruby Fore,Wei Perng,Zachary M Laubach, Darina Czamara,Gemma Sharp,Carrie V Breton,Enrique 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, Regine P M Steegers-Theunissen, Ivana V Yang,Dana Dabelea, Serena Fossati,Ana C Zenclussen, Gunda Herberth, Maria 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 Sebert

Molecular psychiatry(2023)

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摘要
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-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.
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