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

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).

Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology

“…Therefore, the small amount of genetic influence identified in our research (e.g. Barker, Walton et al., in press; Cecil et al., ; Cecil, Walton et al., ) may underestimate genetic variance that could be due to polygenic effects, involving many mQTLs, each of which explains a small amount of variance (as detectable in the ARIES resource given the phenotypes we examined). Another current limitation is that existing array platforms (e.g.…”

“…Twin studies suggest that externalising disorders, such as ODD and ADHD, share considerable common genetic variance (Barker, Cecil, Walton, & Meehan, in press); however, the potential role of DNAm in this common biologic variability is unclear. Based on ARIES, we (Barker, Walton et al., in press) investigated (a) prospective associations between neonatal DNAm (cord blood) and trajectories (ages 7–13) of ODD symptoms, as well as the ODD subdimensions of Irritable and Headstrong; and (b) biological overlap with the ADHD‐associated loci identified by Walton et al. ().…”

Onset and Severity of Early Disruptive Behavioral Disorders in Treatment-Seeking Substance Use Disorder Patients with and without Attention-Deficit/Hyperactivity Disorder

“…An alternative perspective suggests that the ordered sequence (from ODD to CD) is mainly a function of how it represents normative adolescent-driven disruptive behaviors, rather than the product of the disorder expression [48]. The trajectories of the “irritable” and “headstrong” sub-dimensions of ODD and their mechanism overlap with ADHD suggest biological correlates between ODD and ADHD [49]. For instance, ADHD adults with a childhood history of ODD have increased risk for bipolar disorder, anxiety disorders, and SUD, relative to ADHD adults without ODD [50].…”

DRD4 methylation as a potential biomarker for physical aggression: An epigenome‐wide, cross‐tissue investigation

“…However, a gene ontology analysis identified significant enrichment for genes involved in a range of central nervous system processes. As would be expected for brain‐based phenotypes, epigenetic alterations in genes involved in neural function have also been observed in psychiatric disorders that feature aggression as a diagnostic criterion, such as childhood disruptive behavior disorders (Barker et al, ; Cecil et al, ), IED (Montalvo‐Ortiz, Zhang, Chen, Liu, & Coccaro, ), and ASPD (Beach, Brody, Todorov, Gunter, & Philibert, ; Checknita et al, ).…”