DNA methylation profile of individuals with attention deficit hyperactivity disorder (ADHD) performed by array and MLPA techniques

Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood behavioral syndrome that affects approximately 5.3% of children worldwide. Due to its etiological complexity, no consistent biological markers for ADHD have been found so far. However, its high heritability indicates a strong influence of genetic factors. Recent studies have pointed to the involvement of epigenetic processes in ADHD etiology. DNA methylation is one of the major epigenetic mechanisms and is generally related to transcriptional silencing of genes in CpGs islands, which may be associated with gene promoters, gene bodies and untranslated regions (5\' and 3\' UTRs). Thus, we investigated whether ADHD genetic alterations may be related to DNA methylation by performing peripheral blood DNA methylation profiles. In this study, we recruited individuals (n = 29) between 06 and 14 years old with clinical diagnosis of ADHD to participate in the study. The recruitment was performed at \"Núcleo de Atendimento Neuropsicológico Infantil Interdisciplinar\" (NANI), \"Universidade Federal de São Paulo\" (UNIFESP). Children (n = 11) aged 6 to 11 years with negative clinical diagnosis for ADHD were selected for the study as controls. Peripheral blood samples from individuals with and without ADHD were collected for lymphocyte DNA extraction and subsequent realization of methylation array, SNP array and methylation MLPA techniques. Methylation arrays data were processed and analyzed using specific R packages. SNP arrays were analyzed using BlueFuse. MLPAs methylation data were analyzed in GeneMarker. Regarding the results, we can highlight \"Dopaminergic synapse\" pathway as an important finding obtained by the enrichment based on comparative analysis of methylation arrays between ADHD and Control groups. Such a finding corroborates other studies whose evidence indicates a strong genetic association between the dopaminergic pathways and ADHD. Thus, further epigenetic studies are essential to better understand the role of DNA methylation in ADHD etiology (AU)