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	Kustanovich V, 200312660803
Citation	Kustanovich V., Merriman B., McGough J., McCracken J. T., Smalley S. L. and Nelson S. F. (2003) "Biased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder." Mol Psychiatry, 8(3): 309-15.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	113 families with 207 affected children
Predominant Ethnicity	Caucasian
Population	USA
Gender	266 (73% male)
Age Group	Children/Adolescents : mean age=10.6 years (SD=3.5)

Detail Info

Summary	In this paper, they test biased transmission of the 3' UTR SNAP-25 haplotype using a larger ADHD sample of 113 families with 207 affected children. Using the transmission disequilibrium test (TDT), they found a trend consistent with biased transmission of the TC haplotype of SNAP- 25 in all transmissions and detected a significant distortion (P=0.027) when paternal transmissions were evaluated.
Total Sample	Details about subject recruitment have been previously published. Most of our families have multiple affected siblings (69%) and many have an affected parent (46%). From a total sample of 264 such families collected, 202 were used for this study, subselected only because they were collected earliest and thus their DNA samples were fully prepared at the time of this genotyping project. Of the original 202 families, 126 families had definite, Mendelian consistent genotypes in both parents and at least one child for both SNAP25T1065G and SNAP25T1069C. From these, unambiguous haplotype assignments were constructed for 113 families (90%) by the above procedure.
Sample Collection	Details about subject recruitment have been previously published.
Diagnosis Description	All child and adolescent probands were assessed by an interview with the mother using the K-SADS-PL structured interview, followed by direct interview of probands aged 8 years or older. The structured interviews were supplemented with teacher and parent rating scales (SNAP-IV, CBCL, TRF). Of the cases that were used in this study, 50% of the children were of the combined subtype, 8% were of the hyperactive subtype, and 42% were of the inattentive subtype.
Technique	Blood samples were collected for each family member, and genomic DNA was isolated using the Puregene Kit (Gentra Systems, Minneapolis, MN, USA), according to the manufacturer's directions. SNP genotypes were determined using the fluorescence polarization assay. Samples were processed in a 96- well microtiter plate format. Haplotype alleles for the combination of the two SNPs were assigned by imposing Mendelian inheritance consistency on the SNP genotype data.
Analysis Method	All statistical tests were performed using custom programs written in Mathematica (Wolfram Research Inc., IL, USA). Significant results were verified using the sib_tdt program of ASPEX.
Result Description	they found a trend consistent with biased transmission of the TC haplotype of SNAP-25 in all transmissions and detected a significant distortion (P=0.027) when paternal transmissions were evaluated

SNPs reported by this study (count: 2)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs1051312	T/C		allelic TDT P-value=0.420, allelic TDT P-value=0.131 for paternal transmission	TDT of individual alleles did not reach statistical signific...... TDT of individual alleles did not reach statistical significance More...	Non-significant
rs3746544	T/G		allelic TDT P-value=0.085, allelic TDT P-value=0.012 for paternal transmission	TDT of individual alleles did not reach statistical signific...... TDT of individual alleles did not reach statistical significance but paternal transmissions show significant biased transmission of the T allele More...	Significant

Genes reported by this study (count: 1)