title: Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children.
abstract: BACKGROUND
  Attention deficit hyperactivity disorder (ADHD) has a strong genetic component. The study is aimed to test the association of 34 polymorphisms with ADHD symptomatology considering the role of clinical subtypes and sex in a Spanish population.
  
  
  METHODS
  A cohort of ADHD 290 patients and 340 controls aged 6-18 years were included in a case-control study, stratified by sex and ADHD subtype. Multivariate logistic regression was used to detect the combined effects of multiple variants.
  
  
  RESULTS
  After correcting for multiple testing, we found several significant associations between the polymorphisms and ADHD (p value corrected ≤0.05): (1) SLC6A4 and LPHN3 were associated in the total population; (2) SLC6A2, SLC6A3, SLC6A4 and LPHN3 were associated in the combined subtype; and (3) LPHN3 was associated in the male sample. Multivariable logistic regression was used to estimate the influence of these variables for the total sample, combined and inattentive subtype, female and male sample, revealing that these factors contributed to 8.5, 14.6, 2.6, 16.5 and 8.5 % of the variance respectively.
  
  
  CONCLUSIONS
  We report evidence of the genetic contribution of common variants to the ADHD phenotype in four genes, with the LPHN3 gene playing a particularly important role. Future studies should investigate the contribution of genetic variants to the risk of ADHD considering their role in specific sex or subtype, as doing so may produce more predictable and robust models.
authors.affiliation: Department of Genetics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. clara.gomez@idcsalud.es.|Centre for Biomedical Research on Rare Diseases (CIBERER), C/Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain. clara.gomez@idcsalud.es.
authors.forename: Clara I
authors.initials: CI
authors.lastname: Gomez-Sanchez
authors.affiliation: Department of Genetics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. rriveiro@fjd.es.|Centre for Biomedical Research on Rare Diseases (CIBERER), C/Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain. rriveiro@fjd.es.
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.affiliation: Department of Pediatrics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. victor.soto@idcsalud.es.
authors.forename: Victor
authors.initials: V
authors.lastname: Soto-Insuga
authors.affiliation: Department of Pediatrics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. mrodrigomo@fjd.es.
authors.forename: Maria
authors.initials: M
authors.lastname: Rodrigo
authors.affiliation: Department of Pediatrics, La Paz University Hospital, Paseo de la Castellana 261, 28046, Madrid, Spain. ptiradorequero@gmail.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: Tirado-Requero
authors.affiliation: Department of Epidemiology, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. imahillo@fjd.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mahillo-Fernandez
authors.affiliation: Clinical Pharmacology Department, Instituto de Investigación Sanitaria Princesa (IP), Hospital Universitario de la Princesa, C/Diego de Leon 62, 28006, Madrid, Spain. francisco.abad@salud.madrid.org.
authors.forename: Francisco
authors.initials: F
authors.lastname: Abad-Santos
authors.affiliation: Department of Psychiatry, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. jjcarballo@fjd.es.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Carballo
authors.affiliation: Clinical Research, BUC (Biosciences UAM + CSIC) Program, International Campus of Excellence, Universidad Autónoma de Madrid, Ciudad Universitaria de Cantoblanco, 28049, Madrid, Spain. rafael.dalre@fuam.uam.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Dal-Ré
authors.affiliation: Department of Genetics, IIS-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Avda. Reyes Católicos 2, 28040, Madrid, Spain. cayuso@fjd.es.|Centre for Biomedical Research on Rare Diseases (CIBERER), C/Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain. cayuso@fjd.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: C513284:ADGRL3 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C493227:SLC6A2 protein, human; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins