Study Report

Basic Info
Reference |
De Luca V, 2004 (a)14681910
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Citation |
De Luca V., Muglia P., Jain U. and Kennedy J. L. (2004) "No evidence of linkage or association between the norepinephrine transporter (NET) gene MnlI polymorphism and adult ADHD." Am J Med Genet B Neuropsychiatr Genet, 124B(1): 38-40.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
128 nuclear families |
Predominant Ethnicity |
Caucasian |
Population |
Canada |
Age Group |
Adults
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Detail Info
Summary |
The aim of this study was to investigate for the presence of linkage disequilibrium between the MnlI RFLP in the NET gene and adult ADHD in a sample of nuclear families. The MnlI polymorphism was typed in 128 trios and analyzed using the transmission disequilibrium test (TDT). There was no preferential transmission of either allele (X2=0.209, df=1, P=0.647). |
Total Sample |
For this sample there was no deviation from Hardy-Weinberg equilibrium. Of the 128 triads comprising the total sample, 43 were informative for the TDT. |
Sample Collection |
For this study, 128 nuclear families identified through an adult ADHD proband were recruited from the Adult and Adolescent ADHD Research Program of the Centre for Addiction and Mental Health (CAMH). The ethnic makeup was 88% Caucasian, 6% Asian, and 6% African USAn. |
Diagnosis Description |
The diagnosis of ADHD was determined by criteria from the Diagnostic and Statistical Manual-4th edition (DSM-IV) [USAn Psychiatric Association, 1994]. Additional criteria were: >46 on the Wender Utah rating scale (WURS), >55 on the Brown attention deficit disorder scale (BADDRS), >60 on the Conners adult ADHD rating scale (CAARS), >10 on the Conners continuous performance test (CPT), and >80 on block design subtests of Weschler adult intelligence scale-3rd edition (WAIS-III). The structured interview for DSM-IV (SCID-I) [USAn Psychiatric Association, 1994] was employed to document other psychiatric symptoms and comorbid diagnoses. If a comorbid diagnosis emerged as predominating and possibly accounted for the ADHD symptoms then the subject was excluded. Those rating scales were administered by trained interviewers blind with respect to the genotypes of the probands. From all participants and their parents, written informed consent to participate in the study was obtained. |
Technique |
Genomic DNA was extracted form white blood cells using a high salt extraction method. The genotyping was performed with the laboratory staff blind to the psychiatric ratings. The MnlI polymorphism in the NET gene was genotyped as previously reported. |
Analysis Method |
They tested the genotypes from the nuclear families for the presence of linkage disequilibrium between the MnlI polymorphism in NET1 and ADHD with the transmission disequilibrium test (TDT). Separate analysis of the maternal versus paternal transmissions was performed using the extended transmission disequilibrium test (E-TDT). One-way analysis of variance (ANOVA) was used to compare the mean Brown and Wender scores for each of the genotypic classes. They also used the family based association test (FBAT) that allowed the analysis of both qualitative and quantitative traits. They applied FBAT, considering diagnosis of adult ADHD and then the clinically relevant quantitative phenotypes from the Wender and Brown total scores. All the analyses were performed under the assumption of an additive model. |
Result Description |
The TDT showed the G and A allele were transmitted roughly equally to the affected subjects. ETDT revealed that the maternal and paternal transmissions of each allele were not different. The separate analysis for male versus female probands and TDT was not significant for the males and for the females there were not enough informative trios. ANOVA with the Brown Scale total scores revealed no significant difference across the three genotypic classes. Also, the Wender mean scores did not differ significantly among the patients grouped according to genotype. When FBAT was conducted considering the ADHD phenotype as a quantitative trait no association was detected between total scores of the Brown scale, or the WURS score. A slight trend was found for the Brown attention subscale. Given the sample size and the SNP frequencies, a genotype relative risk was estimated as low as 3 to be detectable with >80% of power for a significance level of 0.05. The main results from this study appear to exclude the direct involvement of the MnlI variants of NET1 in the pathogenesis of adult ADHD, as no biased transmission was observed. |

SNPs reported by this study (count: 1)
SNP |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
rs998424 |
G/A |
A |
TDT P-value=0.647, ANOVA P-value=0.941, FBAT P-value=0.48 for Wender, FBAT P-value=0.25 for BDD activation, FBAT P-value=0.17 for BDD attention, FBAT P-value=0.26 for BDD total |
There was no preferential transmission of either allele
There was no preferential transmission of either allele
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Non-significant
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