Spatio-functional annotation of ADHD risk loci in human brain

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. Recent genomic advances have identified genetic loci associated with an increased risk of ADHD. While these loci offer insights into ADHD's genetic underpinnings, understanding their implications in the human brain remains a challenge. This study presents a comprehensive spatio-functional annotation of the recently proposed 27 ADHD risk loci within the human brain.

By utilizing gene enrichment analysis, a method to identify and analyze gene functions and interactions, we can deepen our understanding of the molecular pathways and functional roles of genes linked to ADHD. This analysis uncovers diverse functions among genes associated with ADHD, spanning neuronal activities, transcriptional regulation, receptor signaling, immune responses, and more. Additionally, we explore the spatial context of these genes through the available Hi-C datasets. By examining their spatial localization and potential regulatory interactions, we gain insights into how these risk loci might contribute to ADHD etiology at the chromatin and gene regulation levels.

These findings not only enhance our comprehension of ADHD's genetic basis but may also hold promise for potential future targeted therapeutic strategies. By unraveling the intricate interplay between genetics, brain function, and ADHD, this research opens avenues for precise interventions that could benefit individuals affected by this disorder. Ultimately, this study bridges the gap between genetic discoveries and spatial organization or genome, offering insights into the complexity of ADHD and potential directions for future research.