Neumann, Alexander;
Pingault, Jean-Baptiste;
Felix, Janine F;
Jaddoe, Vincent WV;
Tiemeier, Henning;
Cecil, Charlotte;
Walton, Esther;
(2022)
Epigenome-wide contributions to individual differences in childhood phenotypes: a GREML approach.
Clinical Epigenetics
, 14
, Article 53. 10.1186/s13148-022-01268-w.
Preview |
PDF
s13148-022-01268-w.pdf - Published Version Download (2MB) | Preview |
Abstract
BACKGROUND: DNA methylation is an epigenetic mechanism involved in human development. Numerous epigenome-wide association studies (EWAS) have investigated the associations of DNA methylation at single CpG sites with childhood outcomes. However, the overall contribution of DNA methylation across the genome (R2Methylation) towards childhood phenotypes is unknown. An estimate of R2Methylation would provide context regarding the importance of DNA methylation explaining variance in health outcomes. We therefore estimated the variance explained by epigenome-wide cord blood methylation (R2Methylation) for five childhood phenotypes: gestational age, birth weight, and body mass index (BMI), IQ and ADHD symptoms at school age. We adapted a genome-based restricted maximum likelihood (GREML) approach with cross-validation (CV) to DNA methylation data and applied it in two population-based birth cohorts: ALSPAC (n = 775) and Generation R (n = 1382). RESULTS: Using information from > 470,000 autosomal probes we estimated that DNA methylation at birth explains 32% (SDCV = 0.06) of gestational age variance and 5% (SDCV = 0.02) of birth weight variance. The R2Methylation estimates for BMI, IQ and ADHD symptoms at school age estimates were near 0% across almost all cross-validation iterations. CONCLUSIONS: The results suggest that cord blood methylation explains a moderate degree of variance in gestational age and birth weight, in line with the success of previous EWAS in identifying numerous CpG sites associated with these phenotypes. In contrast, we could not obtain a reliable estimate for school-age BMI, IQ and ADHD symptoms. This may reflect a null bias due to insufficient sample size to detect variance explained in more weakly associated phenotypes, although the true R2Methylation for these phenotypes is likely below that of gestational age and birth weight when using DNA methylation at birth.
| Type: | Article |
|---|---|
| Title: | Epigenome-wide contributions to individual differences in childhood phenotypes: a GREML approach |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13148-022-01268-w |
| Publisher version: | https://doi.org/10.1186/s13148-022-01268-w |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
| Keywords: | ADHD, BMI, Birth weight, Child development, DNA methylation, Epigenetics, GCTA, GREML, Gestational age, IQ, Birth Weight, CpG Islands, DNA Methylation, Epigenesis, Genetic, Epigenome, Genome-Wide Association Study, Humans, Individuality, Phenotype |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10147929 |
Archive Staff Only
 |
View Item |
