In a study, published in Scientific Reports, researchers from the Children’s Hospital of Philadelphia, reported key genetic differences in the causes of attention-deficit hyperactivity disorder (ADHD) between African Americans and individuals of European ancestry. These findings may have an important role to play in determining how patients from different ethnic backgrounds respond to treatments.
ADHD has a prevalence of ~6-8% in children. Male patients outnumber females by almost double. In over two thirds of cases, symptoms persist into adulthood, causing significant life-long impairments. Within the last decade, researchers have attempted to explore the genetic susceptibility of ADHD. Nevertheless, current understanding of this complex trait is incomplete. This is partly due to the broad spectrum of phenotypes seen across ADHD patients.
Most previous studies have largely focused on analysis of coding regions. However, a recent GWAS study, including 20,183 ADHD patients, revealed that variants within non-coding regions were significantly associated with ADHD susceptibility. Moreover, previous studies have also largely included individuals with European ancestry, with little focus on African and other minority populations.
Pathogenesis of ADHD
Researchers used whole-genome sequencing data from 875 individuals to explore the impact of structural variants on ADHD pathogenesis. Specifically, they obtained data from 205 ADHD patients and 670 non-ADHD controls. To expand the analysis to other populations, the team included a significant number of African Americans within the study (116 cases and 408 controls).
The researchers were able to identify multiple structural variants and targets genes that associated with ADHD from previous studies. Most importantly, they were able to also detect 40 novel structural variants in patients with ADHD. Additionally, they identified clustering of structural variants within non-coding regions of pathways involved in neuronal brain function and those highly relevant to ADHD development. The team found that there was little overlap (around 6%) in genes impacted by structural variants between African Americans and individuals of European ancestry. These differences were more significant within non-coding structural variants.
These results suggest that structural variants within non-coding regions may play an important role in ADHD development. Therefore, these variants may also impact how patients respond to ADHD medication.
Hakon Hakonarson, senior author of the study, stated:
“Whole genome sequencing appears to be a valuable discovery tool for studying the molecular mechanisms behind ADHD.
Additionally, the inclusion of African Americans, coupled with the study of non-coding regions of the genome, identified several structural variants that warrant further study, as they may impact both susceptibility to ADHD and how patients respond differently to therapeutic intervention.”
Image credit: By Volodymr Horbovyy – canva.com