Study Report

Basic Info
Reference |
Kustanovich V, 200312660803
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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.
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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)
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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 |
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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...
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Non-significant
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rs3746544 |
T/G |
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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...
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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 |
haplotype TDT P-value=0.027 for paternal transmission, there......
haplotype TDT P-value=0.027 for paternal transmission, there was a trend consistent with biased transmission of the TC haplotype of SNAP-25 in all transmissions and detected a significant distortion when paternal transmissions were evaluated
More...
|
Significant
|