RESUMEN
OBJECTIVE: ADHD consists of a count of symptoms that often presents heterogeneity due to overdispersion and excess of zeros. Statistical inference is usually based on a dichotomous outcome that is underpowered. The main goal of this study was to determine a suited probability distribution to analyze ADHD symptoms in Imaging Genetic studies. METHOD: We used two independent population samples of children to evaluate the consistency of the standard probability distributions based on count data for describing ADHD symptoms. RESULTS: We showed that the zero-inflated negative binomial (ZINB) distribution provided the best power for modeling ADHD symptoms. ZINB reveals a genetic variant, rs273342 (Microtubule-Associated Protein [MAPRE2]), associated with ADHD ( p value = 2.73E-05). This variant was also associated with perivascular volumes (Virchow-Robin spaces; p values < 1E-03). No associations were found when using dichotomous definition. CONCLUSION: We suggest that an appropriate modeling of ADHD symptoms increases statistical power to establish significant risk factors.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/genética , Predisposición Genética a la Enfermedad/genética , Modelos Estadísticos , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Distribución Binomial , Niño , Preescolar , Femenino , Pruebas Genéticas , Genotipo , Humanos , Imagenología Tridimensional/métodos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Distribución de Poisson , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Factores de RiesgoRESUMEN
Recent research indicates that airborne copper exposure in scholar children negatively affects brain functioning. These effects are likely to be influenced by the efficiency of copper metabolism, which is partly regulated by the ATPase copper transporting beta (ATP7B) gene. We investigated whether indoor and outdoor airborne copper exposure is differentially associated with child inattentiveness depending on genetic variation within the ATP7B gene in 1645 scholar children from the BREATHE project. Outdoor (courtyard) and indoor (classroom) air pollution levels were measured during class hours in each school. Inattentiveness was assessed through a follow-up with four measurements via the Attentional Network Test (4475 observations). Linear mixed models considering repeated measures were conducted to assess genetic and exposure main and interaction effects. Two interactions were detected indicating that ATP7B-rs1061472 (P for interaction 0.016) and ATP7B-rs1801243 (P for interaction 0.003) polymorphisms modified the association between indoor copper exposure and inattentiveness. Stratified analysis by genotypes revealed that both outdoor and indoor copper exposure increased inattentiveness in rs1061472-CC and rs1801243-CC carriers. These findings suggest that the genetic background promotes the association between airborne copper exposure at school with inattentiveness in children.