Poster Presentation 43rd Lorne Genome Conference 2022

DNA Methylation of the ST3GAL3 Gene in Attention-Deficit/Hyperactivity Disorder (ADHD) (#148)

Lillian M Dipnall 1 , Mark Ziemann 2 , Jeffrey Craig 3 4 , Timothy J Silk 1 5
  1. Psychology, Deakin University, Burwood, Victoria, Australia
  2. School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, Australia
  3. IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia
  4. Research Institute, Environmental and Genetic Epidemiology Research Group, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
  5. Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia

Background

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder impacting the lives of 5-7% of people globally. Characterised by symptoms of inattention, and/or impulsivity and hyperactivity, ADHD heritability is estimated as 74%. It is possible that a large proportion of unexplained variation could be explained by geneXenvironment interaction. One of the best candidates to explain this phenomenon is epigenetics, as exemplified by DNA methylation. In a recent genome-wide association study of 20,183 ADHD cases and 35,191 controls, the highest-ranked ADHD-associated locus was attributed to the ST3GAL3 gene, which is associated with myelination. This is notable as neuroimaging studies in ADHD have indicated atypical white matter presentation. We aimed to explore the role of ST3GAL3 in ADHD by assessing the relationship of DNA methylation with ADHD diagnostic status and symptom severity

Methods

Sample consisted of saliva from 129 children (Mage=10.40, SDage=0.47; 87 male; 54 ADHD). Diagnosis was confirmed using the NIMH Diagnostic Interview Schedule for Children-Version IV (DISC-IV), symptom severity was quantified with parent-rated Conners 3 ADHD Index. DNA methylation was measured using the Illumina Infinium HumanMethylationEPIC Array. We compared DNA methylation in DNA from saliva in a subset of 78 locations within the ST3GAL3 gene in cases vs controls using linear regression using a suite of Bioconductor packages in R. Models controlled for age, sex, medication status, prenatal alcohol and smoking exposure, socioeconomic status, and cell heterogeneity.

Results

Preliminary results indicate that no locations within the ST3GAL3 gene reached the false discover rate-corrected threshold of 0.05 between ADHD groups and controls. Further, no probes were significantly associated with ADHD symptom severity.

Discussion

Although preliminary results indicate no epigenetic association between ST3GAL3 and ADHD, further analysis is necessary to ensure the robustness of results. Future work aims to investigate the development of myelin in children with ADHD and the role of epigenetics.