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	Comings DE, 19968873217
Citation	Comings D. E., Gade R., Muhleman D., Chiu C., Wu S., To M., Spence M., Dietz G., Winn-Deen E., Rosenthal R. J., Lesieur H. R., Rugle L., Sverd J., Ferry L., Johnson J. P. and MacMurray J. P. (1996) "Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders." Pharmacogenetics, 6(4): 307-18.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	113 ADHD patients and 141 controls for intron 6 G->A TDO2 polymorphism; 108 ADHD patients and 197 controls for intron 6 G->T TDO2 polymorphism; 96 ADHD patients and 135 controls for intron 6 either G->A or G->T TDO2 polymorphism
Predominant Ethnicity	Caucasian
Population	USA

Detail Info

Summary	They have identified four different polymorphisms of the human TDO2 gene. Association studies show a significant association of one or more of these polymorphisms and Tourette syndrome, attention deficit hyperactivity disorder (ADHD) and drug dependence. The intron 6 G->T variant was significantly associated with platelet serotonin levels. Only the association with TS was significant with a Bonferroni correction (p = 0.005). Their purpose here is not to claim these associations are proven, but rather to report preliminary results and show that easily testable polymorphisms are available. They hope to encourage additional research into the potential role the TDO2 gene in these and other psychiatric disorders.
Total Sample	113 ADHD patients and 141 controls for intron 6 G->A TDO2 polymorphism; 108 ADHD patients and 197 controls for intron 6 G->T TDO2 polymorphism; 96 ADHD patients and 135 controls for intron 6 either G->A or G->T TDO2 polymorphism
Sample Collection	The TS probands, TS family members, ADHD probands, two-thirds of the autism probands, and most of the controls were patients, or relatives of patients, treated at the TS and other clinics of the City of Hope National Medical Center (COH).
Diagnosis Description	The diagnoses of TS, chronic motor tic disorder or chronic vocal tic disorder, ADHD and autism, were based on the DSM-III-R (1 987) criteria.
Technique	PCR amplification of the mutant region of intron 6; The PCR product of primers 116 and 117 were ethanol precipitated, and resuspended in TE buffer (Tris HCI 10 mM, EDTA 1 mM); Denaturing gradient gel electrophoresis; Oligonucleotide ligation assay (OLA); Bsl 1 digestion, the identification of the G->T variant by Dpn II digestion, CCCCT repeat amplification and identification of the exon 7 A->C mutation (Asn->His) polymorphism by using PCR.
Analysis Method	The approach used in association studies was to compare the prevalence of various alleles in probands versus unrelated controls, of the same racial group. Bonferonni correction alpha were 0.05/10 or 0.005. The degree of non-random allelic association among the four different polymorphisms studied was estimated by cross-tabulations among subjects where two or more ofthe tests were performed on the same individuals.
Result Description	Association studies show a significant association of one or more of these polymorphisms and Tourette syndrome, attention deficit hyperactivity disorder (ADHD) and drug dependence. The intron 6 G->T variant was significantly associated with platelet serotonin levels. Only the association with TS was significant with a Bonferroni correction (p = 0.005).

Other variant reported by this study (count: 4)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
TDO2 exon7 A(Asn)->C(His)	A/C	C		The prevalence of C allele varied little for subjects with ADHD and not significant.	Non-significant
TDO2 intron5 (CCCCT)n	210-260bp	240bp		The frequencies of alleles at the CCCCT repeat region for case groups were not significantly different from the controls.	Non-significant
TDO2 intron6 G->T	G/T	T	P-value=0.048, X²=3.89, OR=1.78 P-value=0.048, X²=3.89, OR=1.78	The T allele was significantly increased in ADHD probands.	Significant
TDO2 intron6 G->A	G/A	A	P-value is not shown, X²=0.16, OR=0.74 P-value is not shown, X²=0.16, OR=0.74	The A allele was not significantly increased in ADHD probands.	Non-significant

Genes reported by this study (count: 1)