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	Genro JP, 200717044101
Citation	Genro J. P., Zeni C., Polanczyk G. V., Roman T., Rohde L. A. and Hutz M. H. (2007) "A promoter polymorphism (-839 C > T) at the dopamine transporter gene is associated with attention deficit/hyperactivity disorder in Brazilian children." Am J Med Genet B Neuropsychiatr Genet, 144B(2): 215-9.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	243 families
Predominant Ethnicity	Caucasian
Population	Brazil
Gender	82.6% of patients were males
Age Group	Children/Adolescents : mean age 10.3 years (SD=3.1)

Detail Info

Summary	In this study, they tested DAT 3'-UTR VNTR polymorphism and an additional promoter polymorphism -839 C>T (Rs: 2652511) using familybased association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No significant linkage disequilibrium between the two polymorphisms was detected in this sample (D'=0.56; P-value=0.22). No evidence of association with the VNTR polymorphism was found. A significant association (P-value=0.03) for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the ADHD combined type (P-value=0.004). The results suggest a role for the promoter region of DAT1 gene in ADHD susceptibility in this Brazilian sample.
Total Sample	The sample included 243 families comprising 186 parent proband trios and 57 parent-child duos. The first 81 families included in this sample have been previously described by Roman et al. [2001]. Most of them presented the combined type (65.6%), and oppositional defiant disorder was the most common comorbid condition (47%).
Sample Collection	Samples were recruited from the Child and Adolescent Psychiatric Division of the Hospital de Clinicas de Porto Alegre (HCPA). The ADHD patients were predominantly from European descent (92.1%).
Diagnosis Description	A consensus diagnosis of ADHD based on DSM-IV criteria was achieved through a three-stage process, described in detail previously [Roman et al., 2001; Rohde, 2002].
Technique	DNA was extracted from whole blood lymphocytes by a salting out procedure as described by Lahiri and Nurnberger [1991]. The 3'-VNTR polymorphism and promoter polymorphism -839 C>T was amplified using the polymerase chain reaction (PCR), with protocols previously described by Roman et al. [2001] and Rubie et al. [2001], respectively.
Analysis Method	Allele frequencies were estimated by counting. Linkage disequilibrium was estimated using the ARLEQUIN software (version 2.000). Dmax and D' values were calculated as described by Lewontin [1988]. Individual genotype data were analyzed for the complete sample using the statistical package TRANSMIT. Haplotype-based associations were also tested using the TRANSMIT program. The association between genetic markers and disease was also analyzed by the transmission disequilibrium test (TDT) and the Fbat statistics using the FBAT software. A significance level of 5% was accepted in these comparisons.
Result Description	Six alleles were detected at the DAT1 3'-VNTR, and the most common alleles were the 10R and 9R. At the -839 C>T site, allele frequencies in both markers did not show any significant deviation from those expected according to Hardy-Weinberg equilibrium. A significant association for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the combined type only. Biased transmission of the C allele for the combined subtype was also observed in the TDT analyses, using only trios with heterozygous parents. Either on the total sample or on the combined one, no allele was significantly more transmitted than expected for the 3'-VNTR polymorphism in the families with ADHD children. No significant linkage disequilibrium between the 3'-VNTR and the -839 C>T polymorphism was observed in this sample. No association with haplotypes was observed as expected due to non-significant LD.

SNPs reported by this study (count: 1)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs2652511	C/T		Allelic test P-value=0.03 in the total sample, P-value=0.004 in combined type sample, TDT analysis P-value=0.13 in the total sample, P-value=0.03 in combined type sample	A significant association for biased transmission of the C a...... A significant association for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the combined type only. Biased transmission of the C allele for the combined subtype was also observed in the TDT analyses, More...	Significant

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A3 3'-UTR VNTR			Allelic test P-value=0.78 in the total sample, P-value=0.78 ...... Allelic test P-value=0.78 in the total sample, P-value=0.78 in combined type sample; TDT analysis P-value=0.63 in the total sample, P-value=0.42 in combined type sample More...	Either on the total sample or on the combined one, no allele was significantly more transmitted than expected for the 3'-VNTR polymorphism in the families with ADHD children.	Non-significant

Genes reported by this study (count: 1)