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	Manor I, 200818213624
Citation	Manor I., Laiba E., Eisenberg J., Meidad S., Lerer E., Israel S., Gritsenko I., Tyano S., Faraone S. V. and Ebstein R. P. (2008) "Association between tryptophan hydroxylase 2, performance on a continuance performance test and response to methylphenidate in ADHD participants." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1501-8.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	498 affected siblings in 379 families
Predominant Ethnicity	Jews
Population	Israel
Gender	104 females and 394 males
Age Group	Children/Adolescents : 4-18 years

Detail Info

Summary	The main objective of this study was to examine neuropsychological mechanisms mediating the association between tryptophan hydroxylase 2 and attention deficit hyperactivity disorder. A continuous performance test was administered to 344 participants diagnosed with DSM IV ADHD who were also genotyped for eight TPH2 intronic SNPs. Association between TPH2, ADHD, and performance on the T.O.V.A. were tested using robust family-based association tests as implemented in two statistical genetic programs: UNPHASED and PBAT. Association was only observed between an eight locus haplotype and ADHD DSM IV combined type III. Robust association was observed between TPH2 single SNPs (and haplotypes) and performance on the T.O.V.A., especially Errors of Omission. Significant associations were also observed between TPH2 and improvement in T.O.V.A. Total Response Variability scores following acute methylphenidate challenge. Using the MFBAT program, significant multivariate association was observed between single SNPs and haplotypes. The two most common TPH2 eight locus haplotypes were in a Yin Yang configuration and the Yang haplotype was the risk haplotype for both DSM IV ADHD and deficits in neuropsychological performance.
Total Sample	ADHD cases and parents were recruited from the greater Tel-Aviv and Jerusalem municipal areas. Altogether in the current investigation, 498 affected siblings fulfilling DSM IV criteria for ADHD in 379 families that were recruited.
Diagnosis Description	Subjects were all clinical referrals from hospital neurologists, school psychologists, and parents. ADHD criteria followed DSM IV guidelines that recognizes three types of ADHD: (1) ADHDPredominantly Inattentive (Type I), (2) ADHD-Predominantly Hyperactive/Impulsive (Type II), and (3) ADHD-Combined Type (III). 383 combined type, 114 primarily inattentive and 1 hyperactive/impulsive among 498 affected siblings.
Technique	DNA was extracted by Master Pure kit (Epicentre, Madison, WI). Genotyping of six SNPs (rs1386488, rs2220330, rs1386495, rs6582072, rs1386492, and rs4760814) was performed using the SNaPshot MethodTM (Applied BioSystems, CA). Genotyping of the remaining two SNPs (rs1386494 and rs1386497) was performed using realtime PCR with fluorescent resonance energy transfer (FRET) 1502 Manor et al. hybridization probes on the Rotor-Gene 3000 (Corbett Research, Sydney, Australia). For more details, please refer to the original publication.
Analysis Method	Association between the TPH2 polymorphisms and ADHD was tested using the ETDT, a logistic based variant of the transmission disequilibrium test (TDT) which assesses for association (and linkage) without the confounding effect of population stratification.
Result Description	Association was only observed between an eight locus haplotype and ADHD DSM IV combined type III. Robust association was observed between TPH2 single SNPs (and haplotypes) and performance on the T.O.V.A., especially Errors of Omission. Significant associations were also observed between TPH2 and improvement in T.O.V.A. Total Response Variability scores following acute methylphenidate challenge. Using the MFBAT program, significant multivariate association was observed between single SNPs and haplotypes. The two most common TPH2 eight locus haplotypes were in a Yin Yang configuration and the Yang haplotype was the risk haplotype for both DSM IV ADHD and deficits in neuropsychological performance.

SNPs reported by this study (count: 8)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs1386492			P-value>0.05	no significant association no significant association	Non-significant
rs1386494			P-value>0.05	no significant association no significant association	Non-significant
rs1386488			P-value>0.05	no significant association no significant association	Non-significant
rs6582072			P-value>0.05	no significant association no significant association	Non-significant
rs2220330			P-value>0.05	no significant association no significant association	Non-significant
rs4760814			P-value>0.05	no significant association no significant association	Non-significant
rs1386495			P-value>0.05	no significant association no significant association	Non-significant
rs1386497			P-value>0.05	no significant association no significant association	Non-significant

Genes reported by this study (count: 1)