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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(c)17525975
Citation	Brookes K. J., Neale B., Xu X., Thapar A., Gill M., Langley K., Hawi Z., Mill J., Taylor E., Franke B., Chen W., Ebstein R., Buitelaar J., Banaschewski T., Sonuga-Barke E., Eisenberg J., Manor I., Miranda A., Oades R. D., Roeyers H., Rothenberger A., Sergeant J., Steinhausen H. C., Faraone S. V. and Asherson P. (2008) "Differential dopamine receptor D4 allele association with ADHD dependent of proband season of birth." Am J Med Genet B Neuropsychiatr Genet, 147B(1): 94-9.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size
Predominant Ethnicity	Caucasian
Population	Belgium, Germany, the Netherlands, Ireland, Israel, Spain, Switzerland, United Kingdom
Age Group	Children/Adolescents : 4-15 years

Detail Info

Summary	In this study, they investigated the SOB association with ADHD in four independent samples collected for molecular genetic studies of ADHD and found a small but significant increase in summer births compared to a large population control dataset. They also observed a significant association with the 7-repeat allele of the DRD4 gene variable number tandem repeat polymorphism in exon three with probands born in the winter season, with no significant differential transmission of this allele between summer and winter seasons. Preferential transmission of the 2-repeat allele to ADHD probands occurred in those who were born during the summer season, but did not surpass significance for association, even though the difference in transmission between the two seasons was nominally significant. However, following adjustment for multiple testing of alleles none of the SOB effects remained significant. They conclude that the DRD4 7-repeat allele is associated with ADHD but there is no association or interaction with SOB for increased risk for ADHD.
Total Sample	Four independent samples were used, collected by groups in London, Cardiff, Dublin, and the International Multi-centre ADHD Gene (IMAGE) project. Samples include 137 trios from London, 128 trios from Cardiff, 174 trios from Dublin and 671 trios from IMAGE.
Replication Size	137 trios from London, 128 trios from Cardiff, 174 trios from Dublin and 671 trios from IMAGE
Sample Collection	white European origin
Diagnosis Description	DSM-IV operational criteria were applied in each case however no direct comparisons were made to check reliability of diagnosis between the different sites and slightly different protocols applied. Please refer to the original article for detailed descriptions.
Technique	The individual groups gathered DRD4 exon 3 VNTR genotypes and date of birth information separately and data was sent for this analysis to Keeley Brookes in London. For more details, please refer to the original article.
Analysis Method	Each seasonal subset was analyzed using the transmission disequilibrium test (TDT) implemented in the UNPHASED program. Allele-specific tests of association were calculated from the number of transmissions and nontransmission of the 2-, 4-, and 7-repeat alleles from heterozygote parents to their affected offspring for the two seasonal groups. Significant differences between the seasonal groups were tested using the Chi-square test on the number of transmitted (T) and un-transmitted (NT) transmissions for each allele. More details could be found in the original article.
Result Description	the DRD4 7-repeat allele is associated with ADHD but there is no association or interaction with SOB for increased risk for ADHD

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD4 exon3 VNTR	2/4/7 repeat		2R: P-value=0.87, OR=1.08 in London; P-value=0.29, OR=0.68 i...... 2R: P-value=0.87, OR=1.08 in London; P-value=0.29, OR=0.68 in Cardiff; P-value=0.11, OR=1.6 in Dublin; P-value=0.56, OR=0.92 in IMAGE; P-value=0.86, OR=0.97 in combined. 4R: P-value=0.37, OR=0.9 in London; P-value=0.23, OR=1.27 in Cardiff; P-value=0.04, OR=0.74 in Dublin; P-value=0.35, OR=0.92 in IMAGE; P-value=0.17, OR=0.92 in combined. 7R: P-value=0.33, OR=1.2 in London; P-value=0.91, OR=0.97 in Cardiff; P-value=0.2, OR=1.24 in Dublin; P-value=0.09, OR=1.19 in IMAGE; P-value=0.04, OR=1.18 in combined More...	2R is not significantly associated in all samples; significant association was detected in Dublin sample for 4R; 7R is significantly associated with ADHD in the combined dataset	Significant

Genes reported by this study (count: 1)