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	Brookes KJ, 2008(a)18668530
Citation	Brookes K. J., Xu X., Anney R., Franke B., Zhou K., Chen W., Banaschewski T., Buitelaar J., Ebstein R., Eisenberg J., Gill M., Miranda A., Oades R. D., Roeyers H., Rothenberger A., Sergeant J., Sonuga-Barke E., Steinhausen H. C., Taylor E., Faraone S. V. and Asherson P. (2008) "Association of ADHD with genetic variants in the 5'-region of the dopamine transporter gene: evidence for allelic heterogeneity." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1519-23.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	988 affected probands and 150 of their affected siblings
Predominant Ethnicity	Caucasian
Population	Belgium, Germany, the Netherlands, Ireland, Israel, Spain, Switzerland, United Kingdom
Age Group	Children/Adolescents : 5-17 years

Detail Info

Summary	They previously described the importance of a specific haplotype at the 3' end of DAT1, as well as the identification of associated single nucleotide polymorphisms (SNPs) within or close to 5' regulatory sequences. In this study they replicate the association of SNPs at the 5' end of the gene and identify a specific risk haplotype spanning the 5' and 3' markers. These findings indicate the presence of at least two loci associated with ADHD within the DAT1 gene and suggest that either additive or interaction effects of these two loci on the risk for ADHD. Overall these data provide further evidence that genetic variants of the dopamine transporter gene confer an increased risk for ADHD.
Total Sample	the final combined ST1 and ST2 dataset used in this study consisted of 1,147 individuals with DSM-IV combined subtype ADHD from 988 affected probands and 150 of their affected siblings.
Replication Size	376 probands plus 59 affected siblings
Sample Collection	European Caucasian
Diagnosis Description	The diagnosis of ADHD was made following a parent interview with the Parental Account of Child Symptoms interview that asks about ADHD symptoms in various settings. The diagnosis of ADHD was made if sufficient items were identified to fulfill DSM-IV criteria, and both impairment and pervasiveness were present. More details could be found in the original study.
Technique	Genotyping of the 3' UTR and intron 8 VNTRs were previously carried out in the ST2 (replication) sample and the results reported elsewhere [Asherson et al., 2007]. The SNP markers were genotyped using the ABI SNPlex and ABI TaqMan genotyping protocols.
Analysis Method	The transmission disequilibrium test was performed for probands with the combined subtype of ADHD using the UNPHASED program. Nominal evidence for association was determined by P-values less than 0.05 and adjusted significance estimated by permutation tests. In addition we utilized the WHAP program to conduct conditional analyses that test the contribution of genetic variants to haplotype associations.
Result Description	These findings indicate the presence of at least two loci associated with ADHD within the DAT1 gene and suggest that either additive or interaction effects of these two loci on the risk for ADHD.

SNPs reported by this study (count: 4)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs11564750		G	ST1 TDT P-value=0.03, OR=1.35; ST2 TDT P-value=0.004, OR=1.76; ST1&ST2 TDT P-value=0.0006, OR=1.47	showed nominal significance (P<0.01) and surpassed the Bonfe...... showed nominal significance (P<0.01) and surpassed the Bonferroni correction for the four markers tested in ST2; nominally significant associations in the combined analysis of ST1 and ST2 More...	Significant
rs40184		C	ST1 TDT P-value=0.005, OR=1.26; ST2 TDT P-value=0.31, OR=1.13; ST1&ST2 TDT P-value=0.005, OR=1.2	not significantly associated in ST2; nominally significant a...... not significantly associated in ST2; nominally significant associations in the combined analysis of ST1 and ST2 More...	Significant
rs2550946		G	ST1 TDT P-value=0.006, OR=1.24; ST2 TDT P-value=0.45, OR=1.1; ST1&ST2 TDT P-value=0.01, OR=1.19	not significantly associated in ST2; nominally significant a...... not significantly associated in ST2; nominally significant associations in the combined analysis of ST1 and ST2 More...	Significant
rs3776513		G	ST1 TDT P-value=0.05, OR=1.24; ST2 TDT P-value=0.01, OR=1.57; ST1&ST2 TDT P-value=0.009, OR=1.28	showed nominal significance (P<0.01) and surpassed the Bonfe...... showed nominal significance (P<0.01) and surpassed the Bonferroni correction for the four markers tested in ST2; nominally significant associations in the combined analysis of ST1 and ST2 More...	Significant

Genes reported by this study (count: 1)