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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	Lowe N, 2004 (b)14732906
Citation	Lowe N., Kirley A., Hawi Z., Sham P., Wickham H., Kratochvil C. J., Smith S. D., Lee S. Y., Levy F., Kent L., Middle F., Rohde L. A., Roman T., Tahir E., Yazgan Y., Asherson P., Mill J., Thapar A., Payton A., Todd R. D., Stephens T., Ebstein R. P., Manor I., Barr C. L., Wigg K. G., Sinke R. J., Buitelaar J. K., Smalley S. L., Nelson S. F., Biederman J., Faraone S. V. and Gill M. (2004) "Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes." Am J Hum Genet, 74(2): 348-56.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	14 independent samples with 1980 affected cases and 3072 parents
Predominant Ethnicity
Population	USA, Australia, United Kingdom, Brazil, Turkey, Ireland, Israel, Canada, the Netherlands
Age Group	Children/Adolescents

Detail Info

Summary	To establish the postulated association of the (CA)n repeat with ADHD, they collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus. This association appears to be confined to the predominantly inattentive and combined clinical subtypes.
Total Sample	The study included genotypic information from 14 independent samples, with 1980 affected cases and 3072 parents in total
Sample Collection	They collected genotypic information from 14 independent samples of probands and their parents.
Diagnosis Description	All children in the present study were given a diagnosis of one of the three clinical subtypes (predominantly inattentive, predominantly hyperactive/impulsive, or combined) of ADHD, according to criteria of the Diagnostic and Statistical Manual, fourth edition (DSM-IV) (USAn Psychiatric Association 1994). Inclusion criteria for the present study were the presence of a DSM-IV diagnosis of childhood-onset ADHD and the genotyping of one or both parents.
Technique	Genotypic data for the microsatellite marker were collected from each group, along with at least three DNA samples, which were genotyped at the Neuropsychiatry Genetics Laboratory, Dublin, to ensure consistent allele calling between centers. The data received from each group consisted of genotypes from affected probands and either or both of their parents. To obtain as complete a sample as possible-and to avoid potential bias-they contacted all members of the ADHD collaborative network (Faraone et al. 2003) and invited their participation. They also searched PubMed using the keywords 'ADHD' and 'DRD5.'
Analysis Method	Association analyses were performed on each individual group's sample, using the family-based extended transmission/disequilibrium test (ETDT). To test for heterogeneity among the samples, they used the transmission and nontransmission information of the 148-bp allele from the TDT analysis. For the sensitivity analysis, each group's data were removed in turn from the combined total, and the remaining data were reanalyzed. To test the combined sample for significant differences between the diagnostic subtype, the sex of the child, and the sex of the transmitting parent, they first performed TDT analyses on the subsets of each group, using the ETDT. The ORs calculated for each were then weighted according to the number of cases in each subset and were compared with each other by use of logistic regression.
Result Description	The joint analysis showed association with the DRD5 locus (P=0.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD5 5'-flanking (CT/GT/GA)n		148bp	ETDT P-value=0.44, OR=1.5 in group 1; ETDT P-value=0.88, OR=...... ETDT P-value=0.44, OR=1.5 in group 1; ETDT P-value=0.88, OR=1.05 in group 2; ETDT P-value=0.29, OR=0.72 in group 3; ETDT P-value=1, OR=1 in group 4; ETDT P-value=0.77, OR=1.09 in group 5; ETDT P-value=0.21, OR=1.34 in group 6; ETDT P-value=0.28, OR=1.35 in group 7; ETDT P-value=0.42, OR=1.25 in group 8; ETDT P-value=0.05, OR=1.45 in group 9; ETDT P-value=0.02, OR=1.57 in group 10; ETDT P-value=0.004, OR=1.6 in group 11; ETDT P-value=0.38, OR=1.15 in group 12; ETDT P-value=0.75, OR=0.95 in group 13; ETDT P-value=0.05, OR=1.24 in group 14; ETDT P-value=0.00005, OR=1.24, X²=16.45, df=1 in the joint analysis. P-value=0.00007, OR=1.24 in sensitivity analysis for group 1; P-value=0.00004, OR=1.25 in sensitivity analysis for group 2; P-value=0.00002, OR=1.26 in sensitivity analysis for group 3; P-value=0.00004, OR=1.25 in sensitivity analysis for group 4; P-value=0.00007, OR=1.24 in sensitivity analysis for group 5; P-value=0.00011, OR=1.24 in sensitivity analysis for group 6; P-value=0.00009, OR=1.24 in sensitivity analysis for group 7; P-value=0.00007, OR=1.24 in sensitivity analysis for group 8; P-value=0.00027, OR=1.22 in sensitivity analysis for group 9; P-value=0.00041, OR=1.22 in sensitivity analysis for group 10; P-value=0.00103, OR=1.2 in sensitivity analysis for group 11; P-value=0.00007, OR=1.25 in sensitivity analysis for group 12; P-value=0.00001, OR=1.28 in sensitivity analysis for group 13; P-value=0.00039, OR=1.24 in sensitivity analysis for group 14; P-value=0.00005, OR=1.24 in joint analysis of all groups. P-value=0.257, X²=1.287 of predominantly inattentive vs. combined; P-value=0.103, X²=2.654 of predominantly hyperactive/impulsive vs. combined; P-value=0.035, X²=4.468 of predominantly inattentive vs. predominantly hyperactive/impulsive. More...	TDT analyses on the individual samples tested showed a significant association with two of the ADHD samples; a strongly significant association of small effect between ADHD and the 148-bp allele of the microsatellite marker was detected in the joint analysis; sensitivity analysis showed strong significance, regardless of the data set removed; comparison between the individual ORs indicated a significant difference between the inattentive and hyperactive/impulsive subtypes.	Significant

Genes reported by this study (count: 1)