Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P < 1.06 x 10). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10) and BMI in pregnancy (3/914, p = 1.13x10), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Investigators

Emily Oken

Abbreviation

Nat Commun

Publication Date

2019-04-23

Volume

Issue

Page Numbers

1893

Pubmed ID

31015461

Medium

Electronic

Full Title

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Authors

Küpers LK, Monnereau C, Sharp GC, Yousefi P, Salas LA, Ghantous A, Page CM, Reese SE, Wilcox AJ, Czamara D, Starling AP, Novoloaca A, Lent S, Roy R, Hoyo C, Breton CV, Allard C, Just AC, Bakulski KM, Holloway JW, Everson TM, Xu CJ, Huang RC, van der Plaat DA, Wielscher M, Merid SK, Ullemar V, Rezwan FI, Lahti J, van Dongen J, Langie SAS, Richardson TG, Magnus MC, Nohr EA, Xu Z, Duijts L, Zhao S, Zhang W, Plusquin M, DeMeo DL, Solomon O, Heimovaara JH, Jima DD, Gao L, Bustamante M, Perron P, Wright RO, Hertz-Picciotto I, Zhang H, Karagas MR, Gehring U, Marsit CJ, Beilin LJ, Vonk JM, Jarvelin MR, Bergström A, Örtqvist AK, Ewart S, Villa PM, Moore SE, Willemsen G, Standaert ARL, Håberg SE, Sørensen TIA, Taylor JA, Räikkönen K, Yang IV, Kechris K, Nawrot TS, Silver MJ, Gong YY, Richiardi L, Kogevinas M, Litonjua AA, Eskenazi B, Huen K, Mbarek H, Maguire RL, Dwyer T, Vrijheid M, Bouchard L, Baccarelli AA, Croen LA, Karmaus W, Anderson D, de Vries M, Sebert S, Kere J, Karlsson R, Arshad SH, Hämäläinen E, Routledge MN, Boomsma DI, Feinberg AP, Newschaffer CJ, Govarts E, Moisse M, Fallin MD, Melén E, Prentice AM, Kajantie E, Almqvist C, Oken E, Dabelea D, Boezen HM, Melton PE, Wright RJ, Koppelman GH, Trevisi L, Hivert MF, Sunyer J, Munthe-Kaas MC, Murphy SK, Corpeleijn E, Wiemels J, Holland N, Herceg Z, Binder EB, Davey Smith G, Jaddoe VWV, Lie RT, Nystad W, London SJ, Lawlor DA, Relton CL, Snieder H, Felix JF