Maternal Glycemic Dysregulation During Pregnancy and Neonatal Blood DNA Methylation: Meta-analyses of Epigenome-Wide Association Studies
Creators
- Elmar W. Tobi
- Diana L. Juvinao-Quintero
- Justiina Ronkainen
- Raffael Ott
- Rossella Alfano
- Mickaël Canouil
- Madelon L. Geurtsen
- Amna Khamis
- Leanne K. Küpers
- Ives Y. Lim
- Patrice Perron
- Giancarlo Pesce
- Johanna Tuhkanen
- Anne P. Starling
- Toby Andrew
- Elisabeth Binder
- Robert Caiazzo
- Jerry K. Y. Chan
- Romy Gaillard
- Peter D. Gluckman
- Elina Keikkala
- Neerja Karnani
- Sanna Mustaniemi
- Tim S. Nawrot
- François Pattou
- Michelle Plusquin
- Violeta Raverdy
- Kok Hian Tan
- Evangelia Tzala
- Katri Raikkonen
- Christiane Winkler
- Anette-G. Ziegler
- Isabella Annesi-Maesano
- Luigi Bouchard
- Yap Seng Chong
- Dana Dabelea
- Janine F. Felix
- Barbara Heude
- Vincent W. V. Jaddoe
- Jari Lahti
- Brigitte Reimann
- Marja Vääräsmäki
- Amélie Bonnefond
- Philippe Froguel
- Sandra Hummel
- Eero Kajantie
- Marjo-Riita Jarvelin
- Regine P.M. Steegers-Theunissen
- Caitlin G. Howe
- M.F. Hivert
- Sylvain Sebert
Description
Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. To address this hypothesis, we conducted fixed-effects meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmaximum= 3,503), insulin (Nmaximum= 2,062), and area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (Nmaximum = 1,505). Inflation and bias was addressed with the bacon Bioconductor package for individual cohorts and the meta-analysis results and reported model estimates and standard errors are adjusted. Greater maternal AUCgluc during pregnancy was associated with lower cord blood DNAm at neighboring CpGs cg26974062 and cg02988288 in TXNIP. Follow-up analyses show that these changes may have functional and later-life consequences and warrant further mediation and causal analysis.
The corresponding paper can be found here: https://doi.org/10.2337/dc21-1701.
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