title: Assessment of Susceptibility Risk Factors for ADHD in Imaging Genetic Studies.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  We suggest that an appropriate modeling of ADHD symptoms increases statistical power to establish significant risk factors.
authors.affiliation: 1 SGlobal - Centre for Research in Environmental Epidemiology, Barcelona, Spain.|2 Universitat Pompeu Fabra, Barcelona, Spain.|3 CIBER Epidemiología y Salud Pública, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Vilor-Tejedor
authors.affiliation: 1 SGlobal - Centre for Research in Environmental Epidemiology, Barcelona, Spain.|2 Universitat Pompeu Fabra, Barcelona, Spain.|3 CIBER Epidemiología y Salud Pública, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Alemany
authors.affiliation: 1 SGlobal - Centre for Research in Environmental Epidemiology, Barcelona, Spain.|2 Universitat Pompeu Fabra, Barcelona, Spain.|3 CIBER Epidemiología y Salud Pública, Barcelona, Spain.|4 Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Forns
authors.affiliation: 1 SGlobal - Centre for Research in Environmental Epidemiology, Barcelona, Spain.|2 Universitat Pompeu Fabra, Barcelona, Spain.|3 CIBER Epidemiología y Salud Pública, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cáceres
authors.affiliation: 3 CIBER Epidemiología y Salud Pública, Barcelona, Spain.|5 FISABIO-Universitat Jaume I-Universitat de València Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Murcia
authors.affiliation: 6 Hospital del Mar, Cibersam G21, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Macià
authors.affiliation: 6 Hospital del Mar, Cibersam G21, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pujol
authors.affiliation: 1 SGlobal - Centre for Research in Environmental Epidemiology, Barcelona, Spain.|2 Universitat Pompeu Fabra, Barcelona, Spain.|3 CIBER Epidemiología y Salud Pública, Barcelona, Spain.|7 Hospital del Mar Medical Research Institute, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sunyer
authors.affiliation: 1 SGlobal - Centre for Research in Environmental Epidemiology, Barcelona, Spain.|2 Universitat Pompeu Fabra, Barcelona, Spain.|3 CIBER Epidemiología y Salud Pública, Barcelona, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: González
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D016010:Binomial Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D015233:Models, Statistical; D016012:Poisson Distribution; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors
keywords: ADHD symptoms; Imaging Genetics; MAPRE2; Virchow–Robin space; basal ganglia perivascular volumes; childhood; count data; zero-inflated negative binomial