Study Report
Basic Info
Reference |
Lee J, 200817504247
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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.
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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
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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 |
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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
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Non-significant
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rs3787141 |
T/C |
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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...
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Significant
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rs755203 |
G/A |
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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
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Non-significant
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rs2273505 |
G/A |
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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...
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Significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
CHRNA4 |
haplotype GAGC P-value=0.041, X2 =4.161 for all s......
haplotype GAGC P-value=0.041, X2 =4.161 for all subtypes, P-value=0.004, X2 =8.375 in combined subtype; P-value=0.022 in FBAT analysis for hyperactive/impulsive symptoms; CHRNA4 may be involved in ADHD
More...
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Significant
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