Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the <i>ADGRL3</i> (<i>LPHN3</i>), <i>SNAP25</i>, <i>FGF1</i>, <i>DRD4</i>, and <i>SLC6A2</i> genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-<i>SNAP25</i> (T allele; <i>p</i> = 2.46 × 10^-4), rs2282794-<i>FGF1</i> (A allele; <i>p</i> = 1.33 × 10^-2), rs2122642-<i>ADGRL3</i> (C allele, <i>p</i> = 3.5 × 10^-2), and <i>ADGRL3</i> haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, <i>P</i>_permuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by <i>SNAP25</i>, <i>FGF1</i>, and <i>ADGRL3</i> variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.