Children with attention-deficit/hyperactivity disorder (ADHD) who are African American appear to have key genetic differences from those who are Caucasian, and those differences may influence their response to specific medications, according to a genomic-level study published in Scientific Reports.
“We felt as though prior studies of ADHD from a genomic level were not telling the entire story because of whom they were leaving out and what they were studying,” said study senior author Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at the Children’s Hospital of Philadelphia Research Institute, Pennsylvania.
“Given the large number of African American individuals we have recruited into our studies, whose genomes are fundamentally more complex than those of European ancestry, we wanted to see if comparing the coding and noncoding regions of the genome in those of African American and European ancestry could help us pinpoint areas of focus for future research efforts.”
Previous ADHD studies focused mainly on the genome’s coding regions and people with European ancestry. This study, however, considered whole genome sequence data for a total 875 children with and without ADHD: African Americans accounted for 116 of the participants with ADHD and 408 of participants without ADHD.
The study confirmed several structural variants and target genes implicated in ADHD in previous studies but also brought to light 40 novel structural variants in children with ADHD. A cluster of those structural variants occurred in noncoding regions of pathways involved in neuronal brain function and were highly relevant to ADHD development, according to the study, including regulation of gene expression related to specific ADHD phenotypes.
Genes affected by single nucleotide variants showed little overlap—just about 6%—between African American and European ancestry, researchers noted.
“Whole genome sequencing appears to be a valuable discovery tool for studying the molecular mechanisms behind ADHD,” Dr. Hakonarson said. “Additionally, the inclusion of African Americans, coupled with the study of noncoding 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.”
Liu Y, Chang X, Qu H, et al. Non-coding structural variation differentially impacts attention-deficit hyperactivity disorder (ADHD) gene networks in African American vs Caucasian children. Scientific Reports. 2020;10(1):15252.