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	Sheehan K, 200717123708
Citation	Sheehan K., Hawi Z., Gill M. and Kent L. (2007) "No association between TPH2 gene polymorphisms and ADHD in a UK sample." Neurosci Lett, 412(2): 105-7.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	108 ADHD children
Predominant Ethnicity	Caucasian
Population	United Kingdom
Age Group	Children/Adolescents : aged 5-16 years, mean age 11.1 years (SD=3.0)

Detail Info

Summary	Tryptophan Hydroxylase 2 (TPH2) is the rate-limiting enzyme in the biosynthesis of serotonin which is exclusively expressed in the brain. Molecular studies reported significant association between markers mapped to TPH2 and psychiatric conditions including ADHD. They examined four single nucleotide polymorphisms (SNPs) two of which (rs1843809, rs1386493) were reported to associate with ADHD in an Irish ADHD sample. Transmission disequilibrium analysis revealed no significant association between any of these markers and ADHD. Dividing by the sex of the transmitting parent has also failed to replicate the previously reported paternal over-transmission of the associated alleles to ADHD probands. A larger sample size will be required to clarify if TPH2 alleles are or are not associated with ADHD.
Total Sample	The sample consists of 63 parentproband trios, 44 mother-child duos and one father-child duo. Probands were Caucasian, born in the United Kingdom and aged between 5 and 16 years (mean age=11.1 years, S.D.=3.0).
Sample Collection	The sample was recruited from several child psychiatry clinics in the United Kingdom.
Diagnosis Description	Cases were diagnosed using the Child and Adolescent Psychiatric Assessment (CAPA). All probands fulfilled DSM-IV diagnostic criteria for ADHD.
Technique	Genomic DNA was extracted from whole blood or cheek swabs using standard protocols. PCR amplification was carried out in a 12.5ul reaction using 1xPCR reaction buffer containing 10 mM of Tris-HCl (pH 8.9), 50 ng of genomic DNA, 20 pmol of each primer, 200 uM of each dNTP and 0.5U of Taq polymerase. Amplification and cycling conditions for rs1843809 and rs1386493 were performed according to Sheehan et al.
Analysis Method	The transmission disequilibrium test (TDT) was used to assess the relationship between the markers and ADHD. Haplotype based haplotype relative risk (HHRR) was also used owing to the number of duos in the sample. Linkage disequilibrium, measured as D' and r², between the examined SNPs was calculated using the programme Haploview. Haplotype analysis was performed using the program TRANSMIT. All p-values and X² statistics are presented without correction for multiple testing.
Result Description	TDT analysis on full trios was conducted on all of the four examined markers. HHRR analysis was performed on the entire sample and showed no disparity in results obtained for TDT. There is no significant difference in the transmission of alleles to ADHD cases. In addition, dividing the transmission on parental origin also failed to show any significant differences. Linkage disequilibrium (LD), measured as D', shows that the examined markers are in significant LD ranging from 0.51 to 0.96 whereas the r² values ranged from 0.13 to 0.81. The D' findings are comparable to those reported by Sheehan et al. There was no biased transmission of haplotypes to ADHD probands.

SNPs reported by this study (count: 4)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs1386493		C	TDT test: P-value=0.775, OR=0.89 for full trios; P-value=0.815, OR=0.8 for paternal transmission; P-value=1, OR=1 for maternal transmission.	There is no significant difference in the transmission of al...... There is no significant difference in the transmission of alleles to ADHD cases. More...	Non-significant
rs1386496		T	TDT test: P-value=0.636, OR=0.81 for full trios; P-value=0.804, OR=0.77 for paternal transmission; P-value=0.839, OR=0.85 for maternal transmission.	There is no significant difference in the transmission of al...... There is no significant difference in the transmission of alleles to ADHD cases. More...	Non-significant
rs1843809		T	TDT test: P-value=1, OR=1.05 for full trios; P-value=0.302, OR=0.5 for paternal transmission; P-value=0.327, OR=1.6 for maternal transmission.	There is no significant difference in the transmission of al...... There is no significant difference in the transmission of alleles to ADHD cases. More...	Non-significant
rs1386488		A	TDT test: P-value=0.644, OR=1.2 for full trios; P-value=1.2, OR=1 for paternal transmission; P-value=0.557, OR=1.36 for maternal transmission.	There is no significant difference in the transmission of al...... There is no significant difference in the transmission of alleles to ADHD cases. More...	Non-significant

Genes reported by this study (count: 1)