title: Family-based association study of ADHD and genes increasing the risk for smoking behaviours.
abstract: OBJECTIVE
  To investigate five top single nucleotide polymorphisms (SNPs) located in different genes and loci (CHRNA3, BDNF, DBH and LOC100188947) that were highly associated with different dimensions of smoking behaviour, in relation to attention-deficit hyperactivity disorder (ADHD).
  
  
  METHODS
  Cohort study consisting of a clinical sample of children with ADHD.
  
  
  METHODS
  Douglas Institute ADHD Clinic, Montreal, Canada.
  
  
  METHODS
  Families of 454 children with ADHD aged 6-12 years old.
  
  
  METHODS
  Family-based association tests used to study the transmission of risk alleles within these five genetic markers.
  
  
  METHODS
  Clinical diagnosis of ADHD, and a number of behavioural and neurocognitive phenotypes relevant to the disorder.
  
  
  RESULTS
  One SNP (rs1329650) from a non-coding RNA (LOC100188947) was significantly associated with overall ADHD diagnosis with the C* risk allele being over-transmitted from parents to children with ADHD (p=0.02). It was also over-transmitted to children with higher scores on Conners' Parents (p=0.01) and Conners' Teacher (p=0.002) index scores, and Child Behaviour Checklist withdrawn (p=0.001) and aggressive (p=0.007) behaviours. Children with poorer performances on executive and attention tasks were more likely to inherit the risk allele.
  
  
  CONCLUSIONS
  The C* allele of rs1329650 may be increasing the risk for ADHD and smoking behaviour through a common mechanism, possibly externalising behaviours and specific cognitive deficits that manifest as ADHD in childhood and are the gateway to smoking behaviour later in life. This exploratory study illustrates the use of comorbid disorders to investigate ADHD genetics. In spite of its relatively large sample size, replication in future studies is warranted.
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montreal, Quebec, Canada.
authors.forename: Geeta A
authors.initials: GA
authors.lastname: Thakur
authors.forename: Sarojini M
authors.initials: SM
authors.lastname: Sengupta
authors.forename: Natalie
authors.initials: N
authors.lastname: Grizenko
authors.forename: Zia
authors.initials: Z
authors.lastname: Choudhry
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005190:Family; D005819:Genetic Markers; D005838:Genotype; D015438:Health Behavior; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D022661:RNA, Untranslated; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D022661:RNA, Untranslated