Study Report
Basic Info
Reference |
Brophy K, 200212232787
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Citation |
Brophy K., Hawi Z., Kirley A., Fitzgerald M. and Gill M. (2002) "Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population." Mol Psychiatry, 7(8): 913-7.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
93 ADHD nuclear families |
Predominant Ethnicity |
Caucasian |
Population |
Ireland |
Gender |
87% male |
Age Group |
Children/Adolescents
:
aged 4-14 years
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Detail Info
Summary |
Using HHRR and TDT the current study analysed 93 ADHD nuclear families from Ireland and found increased preferential transmission of SNAP-25/DdeI allelel to ADHD cases; HHRR (P=0.01) and linkage (TDT) (P=0.015). In contrast to current findings, Barr et al reported an increased transmission of allele 2 of the DdeI polymorphism though this was not statistically significant. However, they also reported a significantly increased transmission of a haplotype (made of allele 1 of MnlI and allele 2 of the DdeI) in their Canadian ADHD sample. It is not clear what the role of SNAP-25 in ADHD is until these findings are either confirmed or refuted in other ADHD samples. |
Total Sample |
Ninety-three children were assessed from 93 families. Twenty-four families consisted of parent probands and 69 trios consisted of mother, father and affected child. The age range of the probands was between 4 and 14 years, with males accounting for 87%. The families were ethnically Irish with the exception of one family in which the father was Croatian. |
Sample Collection |
ADHD cases were recruited from child psychiatric clinics and schools in West County Dublin and from the Hyperactive and Attention Deficit Children's Support Group of Ireland. |
Diagnosis Description |
Details of diagnosis and clinical criteria can be found in Daly. Briefly, consensus diagnoses were made according to DSM-IV ADHD or UADD either with or without comorbidity. These diagnoses were based on all available clinical information and the rating scales described below. The rating scales used were: (1) the Child Behavioral Checklist (CBCL), a widely based behavioral symptom measure and the records of child behavior problems and social competencies as reported by parents; (2) the Connors Parents and Teachers Rating Scales, 48-item parent and 39-item teacher rating scales; (3) the Comprehensive Teachers Rating Scale (ACTeRS) which includes 24 items relevant to classroom behavior. The 25-item Wender-Utah rating scale (WURS) children was applied to all parents. This rating scale seeks to retrospectively make a diagnosis of ADHD during childhood. A cut-off score of 36 or higher is 96% sensitive and 96% specific for adults with ADHD as children. Familiality, for the purposes of the present study, was defined as the presence of one or more parents with a score on the Wender of >36. |
Technique |
The PCR primer sequences and conditions used to amplify the polymorphisms at the 3' untranslated region of the SNAP-25 gene were those used by Barr et al. Standard PCR reactions were carried out for DNA amplification. |
Analysis Method |
They used the haplotype based haplotype relative risk and transmission disequilibrium test design to avoid any potential population stratification. The Chi-square test and Fisher's exact P were used to assess the significance of the transmission of alleles from parents to their affected children. They also used the programme TRANSMIT to examine haplotypes that might be transmitted more frequently to the ADHD cases and the program EH to assess linkage disequilibrium between the studied markers. They tested the significance of the comparison between preferential maternal and paternal transmissions by plotting 95% confidence intervals and examining for overlap. |
Result Description |
HHRR analysis of 93 ADHD nuclear families was carried out. A significant increase in the transmission of allele 1 of the DdeI polymorphism was observed. No differences in the transmission of the alleles at the polymorphism MnII were observed. Similarly, transmission disequilibrium test (TDT) analysis of the two markers showed a significantly increased transmission of allele 1 of the DdeI polymorphism. However, no distortions in the transmission of the alleles of the MnII polymorphism were observed. Furthermore, when the transmission from parents was considered separately, the association of DdeI polymorphism observed in the total sample was also observed for paternal transmission but not in the maternal sample. However, with the small number of transmissions observed in each group the 95% confidence intervals for the relative risks overlapped suggesting that there is no significant difference between the transmissions by sex of parent. No significant differences in the transmission of the alleles at the MnII polymorphism were observed for paternal or maternal transmissions. Finally, linkage disequilibrium between the two markers was examined using the program EH. A significant disequilibrium for the distribution of the genotypes was observed. However, using the program TRANSMIT showed no preferential transmission of any particular haplotype. |
SNPs reported by this study (count: 2)
SNP |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
rs3746544 |
T/G |
MnlI |
HHRR analysis: overall P-value=0.90, RR=1.01; paternal transmission P-value=0.59, RR=1.1; maternal transmission P-value=1.0, RR=1.0; TDT analysis: overall P-value=0.90, RR=1.06; paternal transmission P-value=1.0, RR=1.08; maternal transmission P-value=1.0, RR=1.0 |
No significant evidence was found for biased transmission
No significant evidence was found for biased transmission
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Non-significant
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rs1051312 |
T/C |
DdeI |
HHRR analysis: overall P-value=0.01, RR=1.51; paternal transmission P-value=0.019, RR=2.0; maternal transmission P-value=0.10, RR=1.45; TDT analysis: overall P-value=0.015, RR=2.13; paternal transmission P-value=0.013, RR=6.0; maternal transmission P-value=0.17, RR=1.9 |
increased preferential transmission was found
increased preferential transmission was found
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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 |
SNAP25 |
increased preferential transmission of SNAP-25/DdeI a......
increased preferential transmission of SNAP-25/DdeI allelel to ADHD cases was found
More...
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Significant
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