Hidden brain genes link ADHD and Parkinson's disease

According to findings published in Nature Genetics, an international research team has identified 254 genetic variants that influence brain structure, potentially offering new insights into conditions like Parkinson's disease and attention-deficit/hyperactivity disorder.

The study, one of the largest studies to examine DNA's relationship with brain volume, analyzed brain scans and genetic data from 74,898 participants to map variations in key areas of the deep brain that control memory, motor skills, and other functions.

Led by researchers from the University of Southern California and QIMR Berghofer Medical Research Institute in Australia, the work is part of the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, which connects more than 1,000 research laboratories across 45 countries.

"A lot of brain diseases are known to be partially genetic, but from a scientific point of view, we want to find the specific changes in the genetic code that cause these," said Paul M. Thompson, associate director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute and principal investigator for ENIGMA.

The research team collected DNA samples and magnetic resonance imaging brain scans from 74,898 participants, examining volume in subcortical regions, including the brainstem, hippocampus, amygdala, and thalamus. These areas play crucial roles in memory formation, emotional regulation, movement control, and sensory processing.

Through genome-wide association studies, GWAS, researchers found genetic variants that explain up to 10% of the observed differences in brain volume among study participants. The findings provide more precise information about which gene variants affect brain volume, particularly in regions linked to specific diseases.

Miguel Rentería, associate professor of computational neurogenomics at QIMR Berghofer and principal investigator of the study, said the research supports the biological basis of conditions like ADHD and Parkinson's disease.

"There is strong evidence that ADHD and Parkinson's have a biological basis, and this research is a necessary step to understanding and eventually treating these conditions more effectively. Our findings suggest that genetic influences that underpin individual differences in brain structure may be fundamental to understanding the underlying causes of brain-related disorders," Rentería said.

The research drew data from multiple sources, including the Cohorts for Heart and Aging Research in Genomic Epidemiology, CHARGE, the UK Biobank, and the Adolescent Brain Cognitive Development (ABCD) study. The National Institutes of Health provided partial funding for the work.

"This paper, for the first time, pinpoints exactly where these genes act in the brain," said Thompson, who holds professorships in multiple departments at USC's Keck School of Medicine, claiming the study creates a potential roadmap for future interventions.

The researchers noted that their findings are correlational, indicating that additional research is needed to establish direct causal links between specific genes and diseases.

The study's first authors were doctoral candidate Luis García-Marín and postdoctoral researcher Adrian Campos from Rentería's research group. USC researchers Neda Jahanshad and Sophia I. Thomopoulos also contributed to the work.

Summary statistics from the study are available for researchers through the ENIGMA consortium. The complete research, including a full list of authors, their affiliations, and funding sources, can be found in the online version of Nature Genetics.

The findings represent a step forward in understanding the genetic foundations of brain structure and development. However, researchers emphasize that more investigation is needed to fully understand how these genetic variations might influence the development or treatment of brain disorders.