Genetic Variation Underpinning ADHD Risk in a Caribbean Community.

Pedro J Puentes-Rozo,Guisselle A García-Llinás,Marco E Anaya-Romero,Antonio Acosta-Hoyos,David A Pineda,Mauricio Arcos-Burgos,Manuel Sánchez-Rojas,Martha L Martínez-Banfi,Martha L Cervantes-Henríquez,Elsy Mejia-Segura,Johan E Acosta-López,Claudio A Mastronardi,Jorge I Vélez,F Xavier Castellanos

doi:10.3390/cells8080907

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 ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 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-SNAP25 (T allele; p = 2.46 × 10−4), rs2282794-FGF1 (A allele; p = 1.33 × 10−2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10−2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 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.

Highlights

Attention deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental behavioural disorder that affects ~5% of children and adolescents of different cohorts worldwide [1,2,3,4,5,6]
We explored the association of ADHD with single nucleotide polymorphisms (SNPs) within these genes in a family-based sample of 386 individuals ascertained from a community inhabiting the city of Barranquilla located in the Caribbean coast of Colombia
We found that markers Synaptosomal-associated protein of molecular weight 25 kDa (SNAP25)-rs362990, Fibroblast growth factor 1 (FGF1)-rs2282794, and ADGRL3-rs2122642 reached statistically significant family-based association test (FBAT) statistics and confer susceptibility to ADHD (Table 3a)

Summary

Introduction

Attention deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental behavioural disorder that affects ~5% (with figures reaching 17%) of children and adolescents of different cohorts worldwide [1,2,3,4,5,6]. Affected individuals are at increased risk of poor educational achievement, low-income, underemployment, legal difficulties, and impaired social relationships [8,9]. ADHD increases the risk for disruptive (externalizing) symptoms of conduct disorder (CD), oppositional defiant disorder (ODD), and substance use disorder (SUD) [8,9]. Genetic factors are strongly implicated in the aetiology of ADHD, CD, ODD, and SUD [6,10–. Common single nucleotide polymorphisms (SNPs) harboured in the Adhesion

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Conclusion