Study Report
Basic Info
Reference |
Brookes KJ, 2006(b)16389200
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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.
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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
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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 64oC (intron 8 VNTR) or 60oC (3' UTR VNTR) for 1 minute and extension 72oC 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 |
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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...
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associated in both populations with global significance |
Significant
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SLC6A3 3'-UTR VNTR |
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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...
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provide global evidence of association and linkage |
Significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
SLC6A3 |
haplotype 10/3 of 3' UTR VNTR and intron 8 VNTR, P-value<0.0......
haplotype 10/3 of 3' UTR VNTR and intron 8 VNTR, P-value<0.001, OR=2.56, X2 =12.25 in the Taiwanese sample and P-value<0.001, OR=2.59, X2 =15.5 in the English sample, a novel association was identified
More...
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Significant
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