Lillian Dipnall et al.
Research indicates that the underlying neurobiology of Attention Deficit/Hyperactivity Disorder (ADHD) may stem from a combination of genetic and environmental contributions. Genetic and epigenetic research have highlighted the potential role of the sialtransferase gene ST3GAL3 in this process. Adopting a pathways approach, this study sought to examine the role that ST3GAL3 and other sialic acid metabolism (SAM) genes play in ADHD. Peripheral measures of DNA methylation (Illumina 850k EPIC; saliva samples) and clinical data were collected as part of a community-based pediatric cohort consisting of 90 children with ADHD [mage= 10.40 (0.49); 66% male] and 50 non-ADHD controls [mage= 10.40 (0.45); 48% male]. Using Reactome, 33 SAM genes were defined and resulted in a total of 1419 probes which included associated promotor/enhancer regions. Linear regression analysis was undertaken to explore differences in SAM probe DNA methylation between children with and without ADHD. The relationship with ADHD symptom severity was also examined. Analysis found 38 probes in the group-regression, and 64 probes in the symptom severity regression reached significance at an uncorrected level (a = 0.05). No probes survived correction for multiple comparisons. Enrichment analysis revealed an overall pattern of hypermethylation across the SAM pathway for the ADHD group, with 84% of nominally significant probes being annotated to sialyltransferase genes. These results suggest that ST3GAL3 and the broader SAM pathway could contribute to subtly disrupted epigenetic regulation in ADHD. However, extensive longitudinal research, across broad developmental age ranges, is necessary to further explore these findings.
