Epigenetic profiling of ADHD symptoms trajectories
a prospective, methylome-wide study
Walton, E, Pingault, J-B, Cecil, CAM, Gaunt, T, Relton, C, Mill, J & Barker, ED, 2017, Epigenetic profiling of ADHD symptoms trajectories: a prospective, methylome-wide study. Molecular Psychiatry, vol 22., pp. 250-256
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent developmental disorder, associated with a range of long-term impairments. Variation in DNA methylation, anepigenetic mechanism, is implicated in both neurobiological functioning and psychiatrichealth. However, the potential role of DNA methylation in ADHD symptoms is currentlyunclear. In this study, we examined data from the Avon Longitudinal Study of Parents andChildren (ALSPAC) – specifically the subsample forming the Accessible Resource forIntegrated Epigenomics Studies (ARIES) – which includes (i) peripheral measures of DNAmethylation (Illumina 450k) at birth (n=817, 49% male) and age 7 (n=892, 50% male) and(ii) trajectories of ADHD symptoms ( 7-15 yrs). We first employed a genome-wide analysisto test whether DNA methylation at birth associates with later ADHD trajectories; and thenfollowed up at age 7 to investigate the stability of associations across early childhood. Wefound that DNA methylation at birth differentiated ADHD trajectories across multiplegenomic locations, including probes annotated to SKI (involved in neural tube development),ZNF544 (previously implicated in ADHD), ST3GAL3 (linked to intellectual disability) andPEX2 (related to perixosomal processes). None of these probes maintained an associationwith ADHD trajectories at age 7. Findings lend novel insights into the epigenetic landscape ofADHD symptoms, highlighting the potential importance of DNA methylation variation ingenes related to neurodevelopmental and peroxisomal processes, which play a key role in thematuration and stability of cortical circuits.
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