Shared genetic background between children and adults with attention deficit/hyperactivity disorder

Abstract

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.Neuropsychopharmacology (2020) 0:1-10; https://doi.

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

“…In this study, the researchers were able to identify nine loci, containing genes involved in brain development, associated with ADHD persistence into adulthood. A significant genetic correlation between ADHD in childhood and its persistent ADHD in adulthood was found, in which also childhood ADHD-PRSs were associated with persistent ADHD 59 . Lastly, though not significant after multiple testing corrections, in the pathway analysis of persistent ADHD adults, nominal significant association to the "reactome energy-dependent regulation of mTOR by LKB1/AMPK", "biocarta mTOR pathway", and "reactome mTORC1-mediated signaling" was found 59 .…”

“…Interestingly, Rovira and colleagues 59 reported recently a shared contribution of common SNPs in childhood ADHD and persistent adults in a meta-analysis of databases from large cohorts of ADHD children and persistent ADHD adults. In this study, the researchers were able to identify nine loci, containing genes involved in brain development, associated with ADHD persistence into adulthood.…”

Genetics of ADHD: What Should the Clinician Know?

“…A recent meta-analysis in more than 17,000 cases showed a high overlap in genetic correlation between children and adults as well as continuous measures as well as categorical ADHD definition [28]. There, genetic factors influencing ADHD persistence in adults (6532 patients with ADHD and 15,874 healthy controls) and early childhood ADHD (10,617 children with ADHD and 16,537 healthy controls) were compared.…”

Epigenome-wide association study of attention-deficit/hyperactivity disorder in adults

“…Recent evidence supports a large genetic overlap between ADHD in children and adults 29 , but little is known about the co-occurrence between the epigenetic signatures characterizing both groups of age. In addition, although various studies report shared genetics between ADHD and several psychiatric and behavioral traits 4,29 , this overlap has not been assessed yet using epigenome-wide data.…”