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	Adams J, 200414699423
Citation	Adams J., Crosbie J., Wigg K., Ickowicz A., Pathare T., Roberts W., Malone M., Schachar R., Tannock R., Kennedy J. L. and Barr C. L. (2004) "Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region." Mol Psychiatry, 9(5): 494-9.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	183 nuclear families with 229 affected children
Predominant Ethnicity	Caucasian
Population	Canada
Age Group	Children/Adolescents : aged 7-16 years

Detail Info

Summary	A follow-up study of the first genome scan for ADHD identified significant evidence for linkage to the 16p13 region. The glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the NMDA receptor, resides in this region and a recent study has reported an association between this gene and ADHD. They tested for linkage between the alleles and haplotypes of four polymorphisms at the GRIN2A locus and ADHD in our sample of 183 nuclear families with 229 affected children. In contrast to previous findings, they did not identify any evidence for a relationship of these markers and ADHD. Owing to the role of GRIN2A in aspects of cognition, they investigated the relationship of this gene to the cognitive phenotypes of inhibitory control, verbal short-term memory and verbal working memory. There was no significant evidence of linkage between GRIN2A and these phenotypes. While the results were not significant in our sample, the previous association finding suggests that further study of this gene is warranted.
Total Sample	183 nuclear families with 229 affected children
Sample Collection	Probands and affected siblings between the ages of 7 and 16 years were recruited from the Child Development and Neuropsychiatry Clinics at the Hospital for Sick Children, and met the Diagnostic and Statistical Manual of Mental Disorder, 4th Edition (DSM-IV) criteria for ADHD.
Diagnosis Description	Probands and affected siblings between the ages of 7 and 16 years were recruited from the Child Development and Neuropsychiatry Clinics at the Hospital for Sick Children, and met the Diagnostic and Statistical Manual of Mental Disorder, 4th Edition (DSM-IV) criteria for ADHD. All children were free of medication for a minimum of 24 h before assessment and cognitive testing. Details for cognitive phenotype measures, please refer to the original paper.
Technique	Four SNPs were genotyped for this study: Grin2a-503, Grin2a-605, Grin2a-5 and Grin2a-531 located in intron 3, intron 5, exon 6 and exon 14, respectively. The SNPs designated Grin2a-503, Grin2a-605 and Grin2a-531 were genotyped with the ABI 7900-HT Sequence Detection System (Applied Biosystems, Foster City, CA, USA) using the TaqMan 5' nuclease assay for allelic discrimination. Genotypes for the Grin2a-5 polymorphism were determined by restriction enzyme digestion of PCR products.
Analysis Method	For the categorical analysis of ADHD, the extended TDT program (ETDT) was used to test for biased transmission of individual marker alleles. Transmission of haplotypes was analyzed using the program TRANSMIT. Only haplotypes with a frequency above 0.10 were included in the analysis. The two-locus linkage disequilibrium program was used to calculate the coefficient of LD, D' between marker alleles in the parental chromosomes. The FBAT program was used for the analysis of quantitative measures.
Result Description	The allele frequencies for the Grin2a-5 polymorphism reported for the Turic sample (allele 1=0.69, allele 2=0.31) and this sample (allele 1=0.72, allele 2=0.28) are similar. No evidence for biased transmission of alleles at any of the markers was observed. Strong linkage disequilibrium (LD) was observed among polymorphisms Grin2a-605, Grin2a-5 and Grin2a-531, located in intron 5, exon 6 and exon 14, respectively. LD was not observed between the intron 3 polymorphism Grin2a-503, and any of the three downstream markers, indicating that LD does not extend across the entire length of the gene. TDT analysis of haplotypes, using the TRANSMIT program, showed no significant evidence for biased transmission of haplotypes. There was no significant evidence for a relationship between the transmission of alleles and scores of the three cognitive phenotypes inhibitory control, verbal short-term memory and verbal working memory.

SNPs reported by this study (count: 3)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs1070503	C/T	T	ETDT P-value=0.58; FBAT P-value=0.53 for stop-task; FBAT P-value=0.79 for digit span forwards; FBAT P-value=0.98 for digit span backwards	No evidence for biased transmission of alleles, no significa...... No evidence for biased transmission of alleles, no significant evidence for a relationship between the transmission of alleles and scores of the three cognitive phenotypes. More...	Non-significant
rs727605	G/A	A	ETDT P-value=0.94; FBAT P-value=0.47 for stop-task; FBAT P-value=0.94 for digit span forwards; FBAT P-value=0.68 for digit span backwards	No evidence for biased transmission of alleles, no significa...... No evidence for biased transmission of alleles, no significant evidence for a relationship between the transmission of alleles and scores of the three cognitive phenotypes. More...	Non-significant
rs1014531	G/A	A	ETDT P-value=0.36; FBAT P-value=0.92 for stop-task; FBAT P-value=0.14 for digit span forwards; FBAT P-value=0.29 for digit span backwards	No evidence for biased transmission of alleles, no significa...... No evidence for biased transmission of alleles, no significant evidence for a relationship between the transmission of alleles and scores of the three cognitive phenotypes. More...	Non-significant

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
GRIN2A exon6 G/A	G/A	A	ETDT P-value=0.74; FBAT P-value=0.65 for stop-task; FBAT P-v...... ETDT P-value=0.74; FBAT P-value=0.65 for stop-task; FBAT P-value=0.57 for digit span forwards; FBAT P-value=0.78 for digit span backwards More...	No evidence for biased transmission of alleles, no significant evidence for a relationship between the transmission of alleles and scores of the three cognitive phenotypes.	Non-significant

Genes reported by this study (count: 1)