|DOI / URL||link|
|Title (Primary)||Meta-analysis of cell type-sSpecific DNA methylation of childhood attention-deficit/hyperactivity disorder symptoms|
|Author||Meijer, M.; Klein, M.; Caramaschi, D.; Mulder, R.; Cosin, M.; Lu, X.; Zhang, Y.; Röder, S.; Zilich, L.; Huels, A.; Hartman, C.; Snieder, H.; Bustamante, M.; Herberth, G.; Franke, B.; Copeland, B.; Aberg, K.; van den Oord, E.|
|Topic||T9 Healthy Planet|
The interplay of genetic factors and environmental adversities in ADHD can be reflected by cell type-specific DNA methylation (DNAm). Previous methylome-wide association studies (MWAS) for ADHD have been performed in bulk tissue only, where meaningful DNAm signal could be left undetected. We aim to identify cell type-specific DNAm profiles associated with childhood ADHD symptoms.
First, we performed array-based (<850.000 sites) cell type-specific MWAS meta-analyses of childhood ADHD symptoms (age-range 4-13 years) in cord- (N=1543) and peripheral blood (N=2009) from the PACE consortium. Then we expanded the coverage of the epigenome to 28 million sites based on methyl-binding-domain sequencing in peripheral blood (N=583; Great Smoky Mountain Study; mean-age 13.5 years). Using epigenomic deconvolution, DNAm associations in the five major blood cells were calculated.
Associations between DNAm and ADHD symptoms were identified in cord blood monocytes (PDE6B, FDR=0.012), CD8T cells (KCNA3, HAND2, both FDR=0.016), and NK cells (KIFC1, FDR=0.043). In peripheral blood, only CD8T cells (RPL31P11, FDR=4.48*10-6 and KCNJ5, FDR=0.0021) showed associations. In the broader coverage analysis, we detected 24 and 16 significant CpG sites (FDR<0.05) in monocytes and granulocytes, respectively. None of these hits were covered by the arrays, and some overlapping genes showed opposite effect sizes in the different cell types, which signal was masked in bulk tissue. Downstream analyses of gene ontology term enrichment showed consistent results between cord and peripheral blood.
We identified the first ADHD-DNAm associations at a cell type-specific level, bringing us closer to understanding the role of specific cell types in the etiology of ADHD.
|Persistent UFZ Identifier||https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=26188|
|Meijer, M., Klein, M., Caramaschi, D., Mulder, R., Cosin, M., Lu, X., Zhang, Y., Röder, S., Zilich, L., Huels, A., Hartman, C., Snieder, H., Bustamante, M., Herberth, G., Franke, B., Copeland, B., Aberg, K., van den Oord, E. (2022):
Meta-analysis of cell type-sSpecific DNA methylation of childhood attention-deficit/hyperactivity disorder symptoms
Biol. Psychiatry 91 (9 (Suppl.)), S111 - S112