DNA methylation profiles at birth and child ADHD symptoms

Abstract Attention deficit/hyperactivity disorder (ADHD) is a common and highly heritable psychiatric disorder. In addition, early life environmental factors contribute to the occurrence of ADHD. Recently, DNA methylation has emerged as a mechanism potentially mediating genetic and environmental effects. Here, we investigated whether newborn DNA methylation patterns of selected candidate genes involved in psychiatric disorders or fetal growth are associated with ADHD symptoms in childhood. Participants were 426 children from a large population based cohort of Dutch national origin. Behavioral data were obtained at age 6 years with the Child Behavior Checklist. For the current study, 11 regions at 7 different genes were selected. DNA methylation levels of cord blood DNA were measured for the 11 regions combined and for each region separately. We examined the association between DNA methylation levels at different regions and ADHD symptoms with linear mixed models. DNA methylation levels were negatively associated with ADHD symptom score in the overall analysis of all 11 regions. This association was largely explained by associations of DRD4 and 5-HTT regions. Other candidate genes showed no association between DNA methylation levels and ADHD symptom score. Associations between DNA methylation levels and ADHD symptom score were attenuated by co-occurring Oppositional defiant disorder and total symptoms. Lower DNA methylation levels of the 7 genes assessed at birth, were associated with more ADHD symptoms of the child at 6 years of age. Further studies are needed to confirm our results and to investigate the possible underlying mechanism.