Genetic Variation in ADHD-Related Risk Genes in an Indigenous Population of the Amazon

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Population Genomics

Background:

• Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heritable neurodevelopmental disorder.
• Genetic factors contributing to ADHD are not well understood in Indigenous populations.
• Genomic studies often lack representation from diverse ancestral groups.

Purpose of the Study:

• To analyze and characterize genetic variations in 11 ADHD-associated genes within an Indigenous Amazonian sample.
• To compare genetic profiles with reference populations from the 1000 Genomes Project.
• To investigate the genetic distinctiveness of Amazonian Indigenous groups concerning ADHD.

Main Methods:

• Exome data analysis from 64 individuals across 12 Indigenous groups from the Brazilian Amazon.
• Identification and characterization of genetic variants in 11 selected genes.
• Comparison of allele frequencies with continental populations using multidimensional scaling analysis.

Main Results:

• Four novel variants were identified in ADGRL3, DCC, and FOXP2 genes.
• Significant differences in allele frequencies were observed for 56 variants compared to continental populations.
• Multidimensional scaling confirmed genetic differentiation of the Indigenous group.

Conclusions:

• Amazonian Indigenous populations possess a distinct genetic profile for ADHD-associated genes, influenced by evolutionary processes.
• The study identified exclusive variants and significant allele frequency differences, underscoring population-specific genetic architectures.
• Inclusion of underrepresented populations is crucial for a comprehensive understanding of ADHD genetics and human genetic diversity.