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, 2006(b)16389200
Citation	Brookes K. J., Mill J., Guindalini C., Curran S., Xu X., Knight J., Chen C. K., Huang Y. S., Sethna V., Taylor E., Chen W., Breen G. and Asherson P. (2006) "A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy." Arch Gen Psychiatry, 63(1): 74-81.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	English sample: 180 probands and their families; Taiwanese sample: 216 probands and their families
Predominant Ethnicity	Caucasian, Mongoloid
Population	United Kingdom, Taiwan
Gender	English sample: 96% male; Taiwanese sample: 89% male
Age Group	Children/Adolescents : 5-15 years, English sample: mean age 10.41, SD=2.34; Taiwanese sample: mean age 8.96, SD=2.60

Detail Info

Summary	To investigate sources of heterogeneity by refining the DAT1 association using additional markers and investigating gene-environment interaction between DAT1 and maternal use of alcohol and tobacco during pregnancy. Within-family tests of association using 2 repeat polymorphisms in the 3' untranslated region and intron 8 plus additional markers in the English sample. Transmission ratios of risk alleles from heterozygote parents to affected offspring and comparison of the transmission ratios in high- and lowexposure groups for the environmental variables. A novel association was identified between ADHD, the intron 8 polymorphism, and a specific risk haplotype in both English and Taiwanese samples. The risk haplotype showed significant interactions with maternal use of alcohol during pregnancy.
Total Sample	English sample: Samples of DNA were collected from 180 probands with a DSM-IV diagnosis of ADHD combined subtype, from both parents of 116 of the probands, and from the mother alone for 64 of the probands. Taiwanese sample: Samples of DNA were collected from 216 probands with a DSM-IV diagnosis of ADHD, from both parents for 135 of the probands, and from the mother alone for 35 of the probands.
Sample Collection	English sample: white European origin; Taiwanese sample
Diagnosis Description	English sample: Cases were recruited from child behavior clinics in southeast United Kingdom and referred for assessment if they were thought by experienced clinicians to have a diagnosis of the combined subtype of ADHD under DSM-IV criteria, with no significant Axis I comorbidity apart from oppositional defiant disorder and conduct disorder and IQ greater than 70. Only individuals fulfilling the recruitment criteria after completion of research assessments were included in the study. Taiwanese sample: Cases of ADHD were ascertained from child psychiatric clinics in the Chang Gung Memorial Hospital in the Taipei area of Taiwan. After completion of a standard maternal interview, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version,38 and completion of parent and teacher Conners revised rating scales,36 diagnosis was applied according to DSM-IV criteria.
Technique	Standard genotyping assays were followed for the VNTRs, involving 30 cycles of annealing 64^oC (intron 8 VNTR) or 60^oC (3' UTR VNTR) for 1 minute and extension 72^oC for 1 minute. Polymerase chain reaction products were genotyped on 2% agarose gel, checked, and repeated whenever the band pattern was not clear. The SNPs were analyzed with a detection system (Amplifluor; Serologicals Corp, Norcross, Ga) by Kbiosciences and microsatellite markers by means of capillary electrophoresis.
Analysis Method	Within-family tests of association using single and multiple marker-haplotype transmission disequilibrium tests (TDTs) and haplotype-based haplotype relative risk analysis, as well as D' and Cramer V (r2) measures of linkage disequilibrium between genetic markers, were calculated by means of UNPHASED. Confirmatory analyses were performed with WHAP.
Result Description	A novel association was identified between ADHD, the intron 8 polymorphism, and a specific risk haplotype in both English and Taiwanese samples. The risk haplotype showed significant interactions with maternal use of alcohol during pregnancy.

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A3 intron8 VNTR			TDT P-value=0.006 in English group; TDT P-value=0.03 in Taiw...... TDT P-value=0.006 in English group; TDT P-value=0.03 in Taiwanese group More...	associated in both populations with global significance	Significant
SLC6A3 3'-UTR VNTR			TDT P-value=0.003 in English group; TDT P-value=0.001 in Tai...... TDT P-value=0.003 in English group; TDT P-value=0.001 in Taiwanese group More...	provide global evidence of association and linkage	Significant

Genes reported by this study (count: 1)