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	Shim SH, 201020470849
Citation	Shim S. H., Hwangbo Y., Kwon Y. J., Jeong H. Y., Lee B. H., Hwang J. A. and Kim Y. K. (2010) "A case-control association study of serotonin 1A receptor gene and tryptophan hydroxylase 2 gene in attention deficit hyperactivity disorder." Prog Neuropsychopharmacol Biol Psychiatry, 34(6): 974-9.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	78 cases, 107 controls
Predominant Ethnicity	Mongoloid
Population	Korea
Gender	63 boys and 15 girls for cases, 41 boys and 66 girls for controls
Age Group	Children/Adolescents : mean age=9.1,SD=1.4;range=5-14 year

Detail Info

Summary	They investigated the association of serotonin the 1A receptor C-1019G single nucleotide polymorphism (HTR1A C-1019G SNP) and tryptophan hydroxylase 2 gene -703G/T (TPH2 -703G/T) SNP with ADHD. All of the ADHD subjects completed a comprehensive and standardized diagnostic and psychological evaluation battery including the parents' Korean version of the ADHD Rating Scale-IV (ARS). The genotype and allele frequencies of 78 ADHD patients and 107 normal controls were analyzed for 5-HTR1A C-1019G and TPH2 -703G/T. There were statistically significant differences in the genotype distributions and allele frequencies of HTR1A C-1019G between the ADHD group and the control group. The homozygous allele C frequency was significantly higher in ADHD patients than in controls. However, no differences in either genotype distribution or in allele frequencies of TPH2 -703G/T were observed between the ADHD patients and the controls. In the ADHD patients, ANCOVA revealed that there were no significant differences in the subscales and total score between the ADHD probands with the CC genotype and those with the CG and GG genotypes in ARS and the Continuous Performance Test (CPT) when adjusting for age and gender. The odds ratio comparing the CC genotype group with the CG genotype group and the C allele with G was 2.12 and 1.79 respectively. Therefore, genotype CC was associated with higher risk of ADHD. The results suggest that the HTR1A C-1019G SNP may affect susceptibility to ADHD. Further investigation with a larger number of subjects is needed in order to confirm this finding.
Total Sample	The present study included 78 children with ADHD (mean age 9.1,SD=1.4 years; range=5-14 year), consisting of 63 boys and 15 girls. The control group included 107 healthy children (mean age 8.7,SD=2.2 years; range=7-12 year), consisting of 41 boys and 66 girls who were all recruited from the same primary school in Korea.
Sample Collection	ethnically Korean
Diagnosis Description	The diagnostic assessments of psychiatric disorders, including ADHD, were carried out according to DSM-IV criteria, with the Kiddie- Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and the Lifetime-Korean Version (K-SADS-PL-K) used for ADHD subjects (Kim et al., 2004). Individuals with a full-scale IQ lower than 70, neurological disorders, seizure disorders, pervasive developmental disorders, tic disorders, bipolar mood disorders, or psychotic disorders were excluded. Mean IQ score was 102.90 (SD=11.72), with a range of 73 to 126. The mean total ARS score was 27.01 (SD=10.29). With regard to the ADHD subtypes according to theDSM-IVdiagnostic criteria, the combined typewasmost common (61.5%), followed by the inattentive type (15.4%), the not-otherwise-specified type (15.4%), and the hyperactivity-impulsivity type (7.7%).
Technique	DNA was extracted from leUnited Kingdomocytes using a commercial DNA extract kit, Wizard Genomic DNA purification kit (Promega, Madison, WI, USA). The HTR1A C-1019G SNP was genotyped by polymerase chain reaction (PCR) according to the protocol originally described by Hong et al. (2006).
Analysis Method	The presence of Hardy-Weinberg equilibrium was tested by the X²-test; comparisons of genotype and allele frequencies between two groups were carried out for each polymorphism using the X² test; logistic regression analysis was used to determine whether ADHD was influenced by the genes HTR1A and TPH2 after demographic factors (age and gender) were taken into account as covariates; group differences in ADHD patients for the clinical variables involving continuous data using analysis of covariance (ANCOVA), with age and gender as covariates. All statistical analyses were performed with SPSS version 12.0 for Windows.
Result Description	a significant association of HTR1A C-1019G with ADHD; there was a statistically significant difference in the genotype and allele frequencies of HTR1A C-1019G between ADHD patients and normal controls. HTR1A C-1019G SNP may have an important effect on susceptibility to ADHD, and that an increased frequency of the C allele may be associated with ADHD. Such increased frequency may confer increased risk of ADHD. TPH2 -703G/T might not be associated with increased vulnerability to ADHD.

SNPs reported by this study (count: 2)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs4570625	G:T		Multivariate model for genotype 'GG' OR=1.00; genotype 'GT' P-value=0.630 , OR=1.24; genotype 'TT' P-value=0.812, OR=1.13 ; Multivariate model for allele 'G' OR=1.00; allele 'T' P-value=0.814, OR=1.06	no differences in either genotype distribution or in allele ...... no differences in either genotype distribution or in allele frequencies between the ADHD patients and the controls More...	Non-significant
rs6295	G/C		Multivariate model for genotype 'GG' P-value=0.834, OR=0.88; genotype 'CG' OR=1; genotype 'CC' P-value=0.039, OR=2.12; Multivariate model for allele, 'G' OR=1; allele 'C' P-value=0.026, OR=1.79	statistically significant differences in the genotype distri...... statistically significant differences in the genotype distributions and allele frequencies and the homozygous allele C frequency was significantly higher in ADHD patients than in controls More...	Significant

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
HTR1A C-1019G	G/C		Multivariate model for genotype 'GG' P-value=0.834, OR=0.88;...... Multivariate model for genotype 'GG' P-value=0.834, OR=0.88; genotype 'CG' OR=1; genotype 'CC' P-value=0.039, OR=2.12; Multivariate model for allele, 'G' OR=1; allele 'C' P-value=0.026, OR=1.79 More...	statistically significant differences in the genotype distributions and allele frequencies and the homozygous allele C frequency was significantly higher in ADHD patients than in controls	Significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
HTR1A	genotype 'CC' of HTR1A C-1019G is associated with a higher r...... genotype 'CC' of HTR1A C-1019G is associated with a higher risk of ADHD More...	Significant
TPH2	no differences in either genotype distribution or in allele ...... no differences in either genotype distribution or in allele frequencies of TPH2 -703G/T were observed between the ADHD patients and the controls More...	Non-significant