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	Lee J, 200817504247
Citation	Lee J., Laurin N., Crosbie J., Ickowicz A., Pathare T., Malone M., Kennedy J. L., Tannock R., Schachar R. and Barr C. L. (2008) "Association study of the nicotinic acetylcholine receptor alpha4 subunit gene, CHRNA4, in attention-deficit hyperactivity disorder." Genes Brain Behav, 7(1): 53-60.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	264 nuclear families
Predominant Ethnicity	Caucasian
Population	Canada
Gender	81% boys
Age Group	Children/Adolescents : 7-16 years

Detail Info

Summary	In the current study, they used the transmission disequilibrium test (TDT) to investigate four polymorphisms encompassing this region of CHRNA4 for association with ADHD in a sample of 264 nuclear families from Toronto. No significant evidence of biased transmission was observed for any of the marker alleles for ADHD defined as a categorical trait (all subtypes included), although one haplotype showed marginal evidence of under-transmission. No association was found with the ADHD predominantly inattentive subtype or with symptom dimension scores of inattention. On the contrary, nominally significant evidence of association of individual markers was obtained for the ADHD combined subtype and with teacher-rated hyperactivity- impulsivity scores, with the same haplotype being under-transmitted. Based on our results and others, CHRNA4 may be involved in ADHD; however, its role in ADHD symptomatology remains to be clarified.
Total Sample	The study sample comprised 264 nuclear families recruited in the Toronto area, for a total of 313 affected children (81% boys). Both parents were genotyped in 192 families.
Sample Collection	The majority of the families reported their ethnic background to be of European Caucasian descent, while 10% of families were of other or mixed background, including Chinese, African, Indian and Native Canadians.
Diagnosis Description	Diagnosis was based on information from semi-structured interviews of parents [Parent Interview for Child Symptoms (PICS-IV)] (Ickowicz et al. 2006) and teachers [Teacher Telephone Interview(TTIIV)] (Tannock et al. 2002). Clinical information was also obtained from the following standardized questionnaires and assessments: Conners' Parent and Teacher Rating Scales-Revised (Conners 1997), Ontario Child Health Survey Scales-Revised (Boyle et al. 1993), Wide-Range Achievement Test-Revision 3 (Wilkinson 1993). The distribution of the affected children among the three DSM-IV ADHD subtypes was: 14% of the predominantly hyperactive/impulsive subtype, 24% of the predominantly inattentive subtype and 62% of the combined subtype.
Technique	DNA was extracted from blood leUnited Kingdomocytes using a high salt method (Miller et al. 1988). We examined four markers in CHRNA4: rs755203 in the promoter and rs2273505, rs6090384 and rs3787141 in intron 2. rs2273505 and rs6090384 were genotyped by restriction enzyme digest. They were both amplified on the same fragment using the following primers: 5'-CCTGCACCTGAGCCACTG-3' and 5'-ACGCTCTGAATCAACCCTTG- 3'. The markers rs755203 and rs3787141 were genotyped with the ABI 7900-HT Sequence Detection Systems (Applied Biosystems) using the TaqMan 5' nuclease assay for allelic discrimination.
Analysis Method	For categorically defined ADHD, we examined the allelic transmission of markers using the extended TDT program and the haplotype transmission with TRANSMIT version 2.5, using the robust estimator of variance option. Quantitative trait TDT analyses were carried out using the FBAT program version 1.5.5, with the additive model of inheritance
Result Description	No significant evidence of biased transmission was observed for any of the marker alleles for ADHD defined as a categorical trait (all subtypes included), although one haplotype showed marginal evidence of under-transmission. No association was found with the ADHD predominantly inattentive subtype or with symptom dimension scores of inattention. On the contrary, nominally significant evidence of association of individual markers was obtained for the ADHD combined subtype and with teacher-rated hyperactivity- impulsivity scores, with the same haplotype being under-transmitted.

SNPs reported by this study (count: 4)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs6090384	G/A		P-value=0.446, X² (1df)=0.581 in all subtypes; P-value=0.782, X² (1df)=0.077 in inattentive subtype; P-value=0.819, X² (1df)=0.053 in combined subtype	no significant evidence of association no significant evidence of association	Non-significant
rs3787141	T/C		P-value=0.166, X² (1df)=1.921 in all subtypes; P-value=0.439, X² (1df)=0.6 in inattentive subtype; P-value=0.046, X² (1df)=4 in combined subtype; P-value=0.044 in FBAT analysis for hyperactive/impulsive symptoms	nominally significant evidence of association with the ADHD ...... nominally significant evidence of association with the ADHD combined subtype and with teacher-rated hyperactivity- impulsivity scores More...	Significant
rs755203	G/A		P-value=0.837, X² (1df)=0.042 in all subtypes; P-value=0.793, X² (1df)=0.069 in inattentive subtype; P-value=0.578, X² (1df)=0.31 in combined subtype	no significant evidence of association no significant evidence of association	Non-significant
rs2273505	G/A		P-value=0.085, X² (1df)=2.97 in all subtypes; P-value=0.808, X² (1df)=0.059 in inattentive subtype; P-value=0.033, X² (1df)=4.568 in combined subtype; P-value=0.026 in FBAT analysis for hyperactive/impulsive symptoms	nominally significant evidence of association with the ADHD ...... nominally significant evidence of association with the ADHD combined subtype and with teacher-rated hyperactivity-impulsivity scores More...	Significant

Genes reported by this study (count: 1)