Family-based association study of ADHD and genes increasing the risk for smoking behaviours
- 1Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada
- 2Department of Psychiatry, McGill University, Montreal, Quebec, Canada
- 3Department of Human Genetics, McGill University, Montreal, Quebec, Canada
- 4Douglas Mental Health University Institute, Montreal, Quebec, Canada
- Correspondence to Dr Ridha Joober, Douglas Mental Health University Institute, 6875 LaSalle Blvd, Montreal, Quebec H4H 1R3, Canada;
- Accepted 15 August 2012
- Published Online First 29 October 2012
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).
Design Cohort study consisting of a clinical sample of children with ADHD.
Setting Douglas Institute ADHD Clinic, Montreal, Canada.
Patients Families of 454 children with ADHD aged 6–12 years old.
Interventions Family-based association tests used to study the transmission of risk alleles within these five genetic markers.
Main outcome measures 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higher scores on Conners’ Parents (p=0.01) and Conners’ Teacher (p=0.002) index scores, and Child Behaviour Checklist withdrawn (p=0.001) and aggressive (p=0.007) behaviours.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.
Trial Registration Number NCT00483106.