Background
Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts.
Methods
An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Region-based analyses accounting for the correlation between nearby methylation sites were also performed.
Results
One epigenome-wide significant differentially methylated position was detected in the Dunedin study, but meta-analysis did not detect differentially methylated positions that were robustly associated across cohorts. In region-based analyses, six significant differentially methylation regions (DMRs) were identified in the Netherlands Twin Register, 19 in the Dunedin study, and none in the Environmental Risk Longitudinal Twin Study. Of these DMRs, 92% were associated with methylation quantitative trait loci, and 68% showed moderate to large blood-brain correlations for DNA methylation levels. DMRs included six nonoverlapping DMRs (three in the Netherlands Twin Register, three in the Dunedin study) in the major histocompatibility complex, which were associated with expression of genes in the major histocompatibility complex, including C4A and C4B, previously implicated in schizophrenia.
Conclusions
Our findings point at new candidate loci involved in immune and neuronal functions that await further replication. Our work also illustrates the need for further research to examine to what extent epigenetic associations with psychiatric traits depend on characteristics such as age, comorbidities, exposures, and genetic background.
Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Overview publication
| Title | Epigenome-wide Association Study of Attention-Deficit/Hyperactivity Disorder Symptoms in Adults. |
| Date | October 15th, 2019 |
| Issue name | Biological psychiatry |
| Issue number | v86.8:599-607 |
| DOI | 10.1016/j.biopsych.2019.02.016 |
| Authors | |
| Info | BIOS Consortium, Heijmans BT, 't Hoen PAC, van Meurs J, Isaacs A, Jansen R, Franke L, Boomsma DI, Pool R, van Dongen J, Hottenga JJ, van Greevenbroek MMJ, Stehouwer CDA, van der Kallen CJH, Schalkwijk CG, Wijmenga C, Franke L, Zhernakova S, Tigchelaar EF, Slagboom PE, Beekman M, Deelen J, van Heemst D, Veldink JH, van den Berg LH, van Duijn CM, Hofman BA, Isaacs A, Uitterlinden AG, van Meurs J, Jhamai PM, Verbiest M, Suchiman HED, Verkerk M, van der Breggen R, van Rooij J, Lakenberg N, Mei H, van Iterson M, van Galen M, Bot J, Zhernakova DV, Jansen R, Hof PV', Deelen P, Nooren I, 't Hoen PAC, Heijmans BT, Moed M, Franke L, Vermaat M, Zhernakova DV, Luijk R, Bonder MJ, van Iterson M, Deelen P, van Dijk F, van Galen M, Arindrarto W, Kielbasa SM, Swertz MA, van Zwet EW, Jansen R, Hoen P', Heijmans BT |
| Keywords | ADHD, CAARS, DNA methylation, EWAS, Epigenetic, Meta-analysis |
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