Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills.
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ABSTRACT:
SUBMITTER: Caramaschi D
PROVIDER: S-EPMC9126809 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
Publications
Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills.
Caramaschi Doretta D Neumann Alexander A Cardenas Andres A Tindula Gwen G Alemany Silvia S Zillich Lea L Pesce Giancarlo G Lahti Jari M T JMT Havdahl Alexandra A Mulder Rosa R Felix Janine F JF Tiemeier Henning H Sirignano Lea L Frank Josef J Witt Stephanie H SH Rietschel Marcella M Deuschle Michael M Huen Karen K Eskenazi Brenda B Send Tabea Sarah TS Ferrer Muriel M Gilles Maria M de Agostini Maria M Baïz Nour N Rifas-Shiman Sheryl L SL Kvist Tuomas T Czamara Darina D Tuominen Samuli T ST Relton Caroline L CL Rai Dheeraj D London Stephanie J SJ Räikkönen Katri K Holland Nina N Annesi-Maesano Isabella I Streit Fabian F Hivert Marie-France MF Oken Emily E Sunyer Jordi J Cecil Charlotte A M CAM Sharp Gemma G
Molecular psychiatry 20220210 4
Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy c ...[more]
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Project description:BackgroundEpigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis.ObjectiveWe sought to identify differential DNA methylation in newborns and children related to childhood asthma.MethodsWithin the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions.ResultsIn newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2.ConclusionNovel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.
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