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. 2018 Sep;89(5):1839-1855.
doi: 10.1111/cdev.12957. Epub 2017 Sep 20.

A Methylome-Wide Association Study of Trajectories of Oppositional Defiant Behaviors and Biological Overlap With Attention Deficit Hyperactivity Disorder

Edward D Barker  1 , Esther Walton  2 , Charlotte A M Cecil  1 , Richard Rowe  3 , Sara R Jaffee  4 , Barbara Maughan  1 , Thomas G O'Connor  5 , Argyris Stringaris  6 , Alan J Meehan  1 , Wendy McArdle  2 , Caroline L Relton  2 , Tom R Gaunt  2
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A Methylome-Wide Association Study of Trajectories of Oppositional Defiant Behaviors and Biological Overlap With Attention Deficit Hyperactivity Disorder

Edward D Barker et al. Child Dev. 2018 Sep.

Abstract

In 671 mother-child (49% male) pairs from an epidemiological birth cohort, we investigated (a) prospective associations between DNA methylation (at birth) and trajectories (ages 7-13) of oppositional defiant disorder (ODD), and the ODD subdimensions of irritable and headstrong; (b) common biological pathways, indexed by DNA methylation, between ODD trajectories and attention deficit hyperactivity disorder (ADHD); (c) genetic influence on DNA methylation; and (d) prenatal risk exposure associations. Methylome-wide significant associations were identified for the ODD and headstrong, but not for irritable. Overlap analysis indicated biological correlates between ODD, headstrong, and ADHD. DNA methylation in ODD and headstrong was (to a degree) genetically influenced. DNA methylation associated with prenatal risk exposures of maternal anxiety (headstrong) and cigarette smoking (ODD and headstrong).

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Figures

Figure 1
Figure 1
Trajectory of the subdimensions of irritable (above) and headstrong (below). [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 2
Figure 2
Manhattan plot of methylome‐wide results on high oppositional defiant disorder (ODD) trajectory. CpG chromosome positions are plotted against −log10 p values. The dotted line indicates false discovery rate (FDR)‐corrected significance threshold, the solid line indicates Bonferroni‐corrected level of significance. Results were derived using a general linear model between DNA methylation (407,462 probes at birth, cell type, and batch and sex corrected) and ODD trajectories. Only FDR‐corrected probes that also survived winsorizing are reported in the tables and followed forward. [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 3
Figure 3
Overlap analyses for oppositional defiant disorder (ODD) and attention deficit hyperactivity disorder (ADHD; A) and headstrong and ADHD (B). Significantly enriched biological processes for genes shared between ODD, headstrong, and ADHD, based on gene ontology (GO) analysis. Circles represent GO terms that survive false discovery rate correction. The x‐axis represents −log(10) p values. The opacity of the circles indicates level of significance (darker = more significant). The size of the circles indicates the percentage of genes in our results for a given pathway compared to the total number of genes in the same pathway (i.e., larger size = larger %; range = 3.39%–20%). [Color figure can be viewed at http://wileyonlinelibrary.com]
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References

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