ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Thakur G. A., 201223109089
Citation	Thakur G. A., Sengupta S. M., Grizenko N., Choudhry Z. and Joober R. (2012) "Family-based association study of ADHD and genes increasing the risk for smoking behaviours." Arch Dis Child, 97(12): 1027-33.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	454 ADHD subjects
Predominant Ethnicity
Population	Canada
Age Group	Children/Adolescents : aged 6-12 years

Detail Info

Summary	The objective of this study was to investigate five top 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 ADHD. 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.
Total Sample	Families of 454 children with ADHD aged 6-12 years old.
Sample Collection	Four hundred and fifty-four ADHD subjects were sequentially recruited from the Disruptive Behaviour Disorders Programme and the child psychiatry outpatient clinics at the Douglas Mental Health University Institute (DMHUI) in Montreal.
Diagnosis Description	Children were diagnosed with ADHD using DSM-IV criteria and based on clinical interviews of the child and at least one parent by a child psychiatrist. A structured clinical interview of parents using the Diagnostic Interview Schedule for Children-IV (DISC-IV) and school reports were used to corroborate the diagnoses. Mothers were primary informants in most cases. Details about diagnostic procedures have been described elsewhere. Children with a history of Tourette's syndrome, pervasive developmental disorder, or psychosis were excluded.
Technique	DNA was extracted from a blood, buccal swab or saliva sample from each affected child, parents and unaffected siblings, whenever possible. The panel of SNPs was genotyped using Sequenom iPlex Gold Technology. Every plate included duplicates of two reference samples to estimate genotyping error and genotypes were read with 100% accuracy on each of the plates. The genotype distribution of all five markers did not depart from Hardy-Weinberg equilibrium: rs1051730 (p=0.96), rs1028936 (p=0.11), rs1329650 (p=0.12), rs3025343 (p=0.49) and rs6265 (p=0.23).
Analysis Method	Single SNP tests of association were performed using family-based association tests (FBAT) to investigate the association between selected markers with ADHD diagnosis and quantitative phenotypes relevant to ADHD
Result Description	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.

SNPs reported by this study (count: 5)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs1028936	A/C	C	FBAT: Z=-1.44, P=0.15, effect size=0.14	No association with ADHD was found. No association with ADHD was found.	Non-significant
rs3025343	A/G	A	FBAT: Z=0.37, P=0.72, effect size=0.04	No association with ADHD was found. No association with ADHD was found.	Non-significant
rs1329650	A/C	A	FBAT: Z=-2.3, P=0.02, effect size=0.19	This SNP was nominally significantly associated with overall...... This SNP was nominally significantly associated with overall ADHD diagnosis. More...	Significant
rs1051730	C/T	T	FBAT: Z=-1.52, P=0.13, effect size=0.12	No association with ADHD was found. No association with ADHD was found.	Non-significant
rs6265	A/G	A	FBAT: Z=-0.79, P=0.43, effect size=0.07	No association with ADHD was found. No association with ADHD was found.	Non-significant

Genes reported by this study (count: 4)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
DBH	SNP rs3025343 mapped to this gene showed no significant asso...... SNP rs3025343 mapped to this gene showed no significant association with ADHD in this study. More...	Non-significant
LOC100188947	SNP rs1329650 mapped to this gene showed significant associa...... SNP rs1329650 mapped to this gene showed significant association with ADHD in this study. More...	Significant
BDNF	SNP rs6265 mapped to this gene showed no significant associa...... SNP rs6265 mapped to this gene showed no significant association with ADHD in this study. More...	Non-significant
CHRNA3	SNP rs1051730 mapped to this gene showed no significant asso...... SNP rs1051730 mapped to this gene showed no significant association with ADHD in this study. More...	Non-significant