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	Feng Y, 2005(b)16088329
Citation	Feng Y., Crosbie J., Wigg K., Pathare T., Ickowicz A., Schachar R., Tannock R., Roberts W., Malone M., Swanson J., Kennedy J. L. and Barr C. L. (2005) "The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder." Mol Psychiatry, 10(11): 998-1005, 973.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	102 subjects from Irvine and 234 subjects from Toronto
Predominant Ethnicity	Caucasian
Population	Canada, USA
Age Group	Children/Adolescents : Toronto sample: 7-16 years; Irvine sample: not mentioned

Detail Info

Summary	To further investigate this gene, they screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25.
Total Sample	They genotyped DNA from 102 subjects diagnosed with ADHD from Irvine and 234 subjects from Toronto, who were either probands or affected siblings in small nuclear families. The Irvine sample consisted of 99 nuclear families composed of 64 probands with both parents genotyped and 35 families with a single parent genotyped. The Toronto sample consisted of 186 families with an ADHD proband. Of these, 43 families had genotypes available for a single parent and the remainder had DNA genotyped for both parents In all 48 affected siblings were included in the analysis.
Sample Collection	Subjects were collected from The Hospital for Sick Children, Toronto, and the University of California (UC) Irvine Child Development Center in Irvine, CA.
Diagnosis Description	Subjects from The Hospital for Sick Children, Toronto Methods of assessment, characteristics of the subjects, and inclusion and exclusion criteria for the study have been previously described, including the instruments used to collect information for diagnosis of ADHD and comorbid conditions, and to assess academic and language skills. Probands and their siblings were included if they were between 7 and 16 years old, and met DSM-IV criteria for one of the three ADHD subtypes (inattentive, hyperactiveimpulsive, or combined). Of the cases that were used in this study, 58% of the children were of the combined subtype, 14% were of the hyperactive/ impulsive subtype, and 26% were of the primarily inattentive subtype. Probands identified at the University of California (UC) Irvine Child Development Center in Irvine, CA have been previously described. Briefly, subjects were recruited from clinical trials with a diagnosis of combined subtype ADHD by DSM-IV criteria confirmed by a structured interview.
Technique	DNA sequence variants were identified using single strand conformational polymorphism (SSCP) analysis or through public databases (NCBI; http:// www.ncbi.nlm.nih.gov/SNP/index.html, Applied Biosystems, Assays-on-Demands; https://www. appliedbiosystems.com/). For SSCP analyses, primers were designed to screen the entire exon including, as much as possible, the exon/intron boundaries. The genotyping assays for the two restriction enzyme polymorphisms, MnlI (rs3746544) and DdeI (rs1051312), have been previously described. The remaining polymorphisms were genotyped using the 5' nuclease assay (TaqMans), on an ABI 7900 (Applied Biosystems, Foster City, CA, USA) using either commericially available probes and primers (Assays-by-Demands, Applied Biosystems) or probes and primers designed by them for this study. Please refer to the original publication for more details about polymorphism detection and marker genotyping.
Analysis Method	The transmission of the alleles for the transmission disequilibrium test (TDT) was calculated using the extended TDT (ETDT) program, and the transmission of the haplotypes was analyzed with the TRANSMIT program using the robust estimator option. Analyses of behavioral dimensions were carried out using a quantitative TDT as implemented in the FBAT program using an additive model.
Result Description	Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Their findings continue to support SNAP25 in the susceptibility to ADHD.

SNPs reported by this study (count: 11)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs362549	A/G		allelic TDT P-value=0.225, X²=1.473 in Irvine sample; allelic TDT P-value=0.012, X²=6.352 in Toronto sample; TDT P-value=0.612, X²(1df)=0.257 in the Toronto sample by Inattentive subtype; TDT P-value=0.491, X²(1df)=0.474 in the Toronto sample by Hyperactive/impulsive subtype; TDT P-value=0.008, X²(1df)=7.042 in the Toronto sample by Combined subtype	there was significant evidence for biased transmission in th...... there was significant evidence for biased transmission in the Toronto sample; TDT test was not significant in the Irvine sample; the observed evidence for biased transmission was not significant in the inattentive or hyperactive/impulsive subtype, but significant in the combined subtype in the Toronto sample More...	Significant
rs362986	T/C		allelic TDT P-value=0.336, X²=0.925 in Irvine sample; allelic TDT P-value=0.112, X²=2.532 in Toronto sample	there was no significant result both in the Toronto sample a...... there was no significant result both in the Toronto sample and the Irvine sample More...	Non-significant
rs362569	T/C		allelic TDT P-value=0.68, X²=0.17 in Irvine sample; allelic TDT P-value=0.142, X²=2.162 in Toronto sample	there was no significant result both in the Toronto sample a...... there was no significant result both in the Toronto sample and the Irvine sample More...	Non-significant
rs6039806	C/A		allelic TDT P-value=0.302, X²=1.067 in Irvine sample; allelic TDT P-value=0.005, X²=7.848 in Toronto sample; TDT P-value=0.493, X²(1df)=0.471 in the Toronto sample by Inattentive subtype; TDT P-value=0.346, X²(1df)=0.889 in the Toronto sample by Hyperactive/impulsive subtype; TDT P-value=0.007, X²(1df)=7.218 in the Toronto sample by Combined subtype	there was significant evidence for biased transmission in th...... there was significant evidence for biased transmission in the Toronto sample; TDT test was not significant in the Irvine sample; the observed evidence for biased transmission was not significant in the inattentive or hyperactive/impulsive subtype, but significant in the combined subtype in the Toronto sample More...	Significant
rs363006	G/A		allelic TDT P-value=0.304, X²=1.059 in Irvine sample; allelic TDT P-value=0.925, X²=0.009 in Toronto sample	there was no significant result both in the Toronto sample a...... there was no significant result both in the Toronto sample and the Irvine sample More...	Non-significant
rs3746544	T/G		allelic TDT P-value=0.906, X²=0.014 in Irvine sample; allelic TDT P-value=0.813, X²=0.056 in Toronto sample	there was no significant result both in the Toronto sample a...... there was no significant result both in the Toronto sample and the Irvine sample More...	Non-significant
rs362987	A/C		allelic TDT P-value=0.249, X²=1.328 in Irvine sample; allelic TDT P-value=0.039, X²=4.269 in Toronto sample; TDT P-value=0.631, X²(1df)=0.231 in the Toronto sample by Inattentive subtype; TDT P-value=0.819, X²(1df)=0.053 in the Toronto sample by Hyperactive/impulsive subtype; TDT P-value=0.016, X²(1df)=5.841 in the Toronto sample by Combined subtype	there was significant evidence for biased transmission in th...... there was significant evidence for biased transmission in the Toronto sample; TDT test was not significant in the Irvine sample; the observed evidence for biased transmission was not significant in the inattentive or hyperactive/impulsive subtype, but significant in the combined subtype in the Toronto sample More...	Significant
rs362998	C/G		allelic TDT P-value=0.439, X²=0.6 in Irvine sample; allelic TDT P-value=0.019, X²=5.488 in Toronto sample; TDT P-value=0.763, X²(1df)=0.091 in the Toronto sample by Inattentive subtype; TDT P-value=0.014, X²(1df)=6 in the Toronto sample by Combined subtype	there was significant evidence for biased transmission in th...... there was significant evidence for biased transmission in the Toronto sample; TDT test was not significant in the Irvine sample; the observed evidence for biased transmission was not significant in the inattentive or hyperactive/impulsive subtype, but significant in the combined subtype in the Toronto sample More...	Significant
rs1051312	T/C		allelic TDT P-value=0.286, X²=1.14 in Irvine sample; allelic TDT P-value=0.933, X²=0.007 in Toronto sample	there was no significant result both in the Toronto sample a...... there was no significant result both in the Toronto sample and the Irvine sample More...	Non-significant
rs1889189	T/C		allelic TDT P-value=0.508, X²=0.439 in Irvine sample; allelic TDT P-value=0.084, X²=2.988 in Toronto sample	there was no significant result both in the Toronto sample a...... there was no significant result both in the Toronto sample and the Irvine sample More...	Non-significant
rs8636	T/C		allelic TDT P-value=1, X²=0 in Irvine sample; allelic TDT P-value=0.875, X²=0.025 in Toronto sample	there was no significant result both in the Toronto sample a...... there was no significant result both in the Toronto sample and the Irvine sample More...	Non-significant

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SNAP25 intron3 C-2488338-10	G/A		allelic TDT P-value=0.827, X²=0.048 in Irvine sam...... allelic TDT P-value=0.827, X²=0.048 in Irvine sample; allelic TDT P-value=0.199, X²=1.653 in Toronto sample More...	there was no significant result both in the Toronto sample and the Irvine sample	Non-significant

Genes reported by this study (count: 1)