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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	Barr CL, 2001(c)11326305
Citation	Barr C. L., Wigg K., Zai G., Roberts W., Malone M., Schachar R., Tannock R. and Kennedy J. L. (2001) "Attention-deficit hyperactivity disorder and the adrenergic receptors alpha 1C and alpha 2C." Mol Psychiatry, 6(3): 334-7.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	103 nuclear families
Predominant Ethnicity	Caucasian
Population	Canada
Age Group	Children/Adolescents

Detail Info

Summary	In this study they tested the genes for two adrenergic receptors, alpha 1C (ADRA1C) located on chromosome 8p11.2, and alpha 2C (ADRA2C) located on chromosome 4p16, as genetic susceptibility factors in ADHD. For the adrenergic receptor alpha 1C they used a C to T polymorphism that results in a change of Cys to Arg at codon 492 for the linkage study. For the adrenergic receptor alpha 2C gene they examined a dinucleotide repeat polymorphism located approximately 6 kb from the gene. They examined these polymorphisms in a sample of 103 families ascertained through an ADHD proband. Using the transmission disequilibrium test, they did not observe biased transmission of any of the alleles of these polymorphisms. They conclude that the alleles at the polymorphisms tested in these two genes are not linked to the ADHD phenotype in this sample of families.
Total Sample	They used a sample of 103 nuclear families identified through an ADHD proband. Both parents were genotyped in 86 of the families and a single parent was genotyped for 17. The sample also included 28 siblings meeting the same criteria for participation in the study as the probands.
Sample Collection	The assessment and characteristics of the subjects for this study have been previously described.
Diagnosis Description	Subjects were included if they met DSM-IV criteria for ADHD. Information for the diagnosis of ADHD and comorbid conditions was gathered through a semi-structured interview for parents (Parent Interview for Child Symptoms, PICS-IV; Schachar and Ickowicz, unpublished) and teachers (Teacher Telephone Interview-IV, TTI; Tannock and Schachar, unpublished). This information was supplemented with the following questionnaires and child assessments: Conners Parent and Teacher Rating Scales-Revised, the Ontario Child Health Survey Scales-Revised, Wide Range Achievement Test-III, Clinical Evaluation of Language Fundamentals 3rd Edition, Children's Depression Inventory, and Children's Manifest Anxiety Scale.
Technique	DNA was extracted from blood lymphocytes using a high salt extraction method. The ADRA1C PstI polymorphism was genotyped according to Shibata et al. The 502-bp fragment of ADRA1C was amplified using a reaction mixture of 100 ng of genomic DNA, the primers P1 5' atg ctc cag cca aga gtt ca 3' and P2 5' tcc aag aag agc tgg cct tc 3', 1.5 mM MgCl₂, and 1 unit of Taq polymerase. The ADRA2C polymorphism was genotyped as previously described with minor modifications. The 179-193 bp fragment of ADRA2C was amplified using a reaction mixture of 100 ng of genomic DNA, the primers adra2c-1 5' cgc tgc ctc cct tcc acc tgt tg 3' and adra2c-2 5' agt ggg cag ggc ggg gca ggt 3', the PCRx Enhancer System (1xPCR Amplification Buffer, 1xPCRx Enhancer Solution, 1.5 mM MgSO₄ from Gibco BRL (Life Technologies, Gaithersburgh, MD, USA), and 1 unit of Taq polymerase.
Analysis Method	The transmission disequilibrium test (TDT) was calculated using the ETDT program.
Result Description	Using the transmission disequilibrium test, they did not observe biased transmission of any of the alleles of these polymorphisms. They conclude that the alleles at the polymorphisms tested in these two genes are not linked to the ADHD phenotype in this sample of families.

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
ADRA1A Cys492Arg	Cys492/Arg492		allelic P-value=0.225, X²=1.47 allelic P-value=0.225, X²=1.47	no evidence was found for biased transmission of either allele of the ADRA1C polymorphism to the probands in this sample of ADHD families	Non-significant
ADRA2C upstream (TG)n	181bp-191bp		allelic P-value=0.523, X²=0.409 for 183bp; alleli...... allelic P-value=0.523, X²=0.409 for 183bp; allelic P-value=0.68, X²=0.17 for 185bp More...	there was no evidence for biased transmission of any of the alleles of the ADRA2C polymorphism	Non-significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
ADRA1A	no evidence was found for biased transmission of either alle...... no evidence was found for biased transmission of either allele of the ADRA1C polymorphism to the probands in this sample of ADHD families More...	Non-significant
ADRA2C	there was no evidence for biased transmission of any of the ...... there was no evidence for biased transmission of any of the alleles of the ADRA2C polymorphism More...	Non-significant