ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurobehavioral disorder that affects children worldwide, with detrimental long-term consequences in affected individuals. ADHD-affected patients display visual-motor and visuospatial abilities and skills that depart from those exhibited by non-affected individuals and struggle with perceptual organization, which might partially explain impulsive responses. Endophenotypes (quantifiable or dimensional constructs that are closely related to the root cause of the disease) might provide a more powerful and objective framework for dissecting the underlying neurobiology of ADHD than that of categories offered by the syndromic classification. In here, we explore the potential presence of the linkage and association of single-nucleotide polymorphisms (SNPs), harbored in genes implicated in the etiology of ADHD (ADGRL3, DRD4, and FGF1), with cognitive endophenotypes related to working memory and perceptual organization in 113 nuclear families. These families were ascertained from a geographical area of the Caribbean coast, in the north of Colombia, where the community is characterized by its ethnic diversity and differential gene pool. We found a significant association and linkage of markers ADGRL3-rs1565902, DRD4-rs916457 and FGF1-rs2282794 to neuropsychological tasks outlining working memory and perceptual organization such as performance in the digits forward and backward, arithmetic, similarities, the completion of figures and the assembly of objects. Our results provide strong support to understand ADHD as a combination of working memory and perceptual organization deficits and highlight the importance of the genetic background shaping the neurobiology, clinical complexity, and physiopathology of ADHD. Further, this study supplements new information regarding an ethnically diverse community with a vast African American contribution, where ADHD studies are scarce.

Automated summary

ADHD is a highly heritable neurobehavioral disorder affecting children worldwide and individuals affected struggle with visual-motor and visuospatial abilities, potentially contributing to impulsive responses. Endophenotypes may provide a more powerful framework for understanding the neurobiology of ADHD, with this study highlighting the combination of working memory and perceptual organization deficits in ADHD patients.