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	Bhaduri N, 2006 (a)16331654
Citation	Bhaduri N., Das M., Sinha S., Chattopadhyay A., Gangopadhyay P. K., Chaudhuri K., Singh M. and Mukhopadhyay K. (2006) "Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population." Am J Med Genet B Neuropsychiatr Genet, 141B(1): 61-6.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	44 trios and 6 duos and 50 healthy controls
Predominant Ethnicity	Indian
Population	India
Gender	88% male cases
Age Group	Children/Adolescents : 2.4-14 years

Detail Info

Summary	Association of 5' flanking 120-bp duplication, exon 1 12-bp duplication, and exon 3 48-bp variable numbers of tandem repeats (VNTR) were analyzed in 50 ADHD cases. Haplotype-based haplotype relative risk (HHRR) analysis and transmission disequilibrium test (TDT) were carried out to ascertain the association of these polymorphisms with the disorder. Linkage disequilibria (LD) between the polymorphisms were calculated using EHt and 2LD programs. Their preliminary data showed lack of association between ADHD and transmission of the 5' flanking 120-bp duplication and exon 1 12-bp duplication. But, the transmissions of 6 and 7 repeat alleles of exon 3 48-bp VNTR showed significant association with ADHD. They have also examined the haplotype frequencies and biased transmission of one haplotype was observed in ADHD probands. LD analysis showed very strong disequilibrium between exon 1 12-bp duplication and exon 3 48-bp VNTR. Strong LD was also observed between the 5' flanking 120-bp duplication and exon 1 12-bp duplication.
Total Sample	The subjects and their parents comprising 44 complete parent-offspring trios and 6 duos with only 1 parent. The control group comprising 50 ethnically matched healthy individuals.
Diagnosis Description	Diagnoses were made by mental health professionals (child psychiatrist and child psychologist) according to Diagnostic and Statistical Manual-4th edition, Text revised [APA, 2000] followed by psychological evaluation through: (1) The Conners' Parents and Teachers Rating Scale [Conners et al., 1998], and (2) Wechsler Intelligence Scale for Children [Wechsler, 1991] for the inattention-hyperactivity level and IQ status, respectively.
Technique	Genomic DNA was prepared from leUnited Kingdomocytes using the protocol of Miller et al. [1988]. PCR amplification for all the polymorphisms was carried out using Perkin Elmer thermal cycler (Gene Amp #2400). Amplification and analysis of the 5' flanking 120-bp duplication were carried out following the method of Seaman et al. [1999] with minor alterations. PCR amplification of the 12 bp repeat region in exon 1 was done as described by Seaman et al. [2000]. PstI digestion of the PCR product was carried out following the method of Barr et al. [2000]. The 48 bp VNTR region in exon 3 was amplified using primer sets mentioned by Lichter et al. [1993] after minor modification of the protocol.
Analysis Method	Haplotype-based haplotype relative risk (HHRR) analysis as well as transmission disequilibrium test (TDT) was used to ascertain association between ADHD and transmission of genetic polymorphisms. The EH+ program, version 1.2 was utilized to estimate the haplotype frequencies for different alleles of 50 flanking 120-bp duplication, exon 1 12-bp duplication, and exon 3 48-bp VNTR. Subsequently, the two-locus linkage disequilibrium (2LD) calculator, was used to compute the disequilibria values for all three polymorphisms.
Result Description	Their preliminary data showed lack of association between ADHD and transmission of the 5' flanking 120-bp duplication and exon 1 12-bp duplication. But, the transmissions of 6 and 7 repeat alleles of exon 3 48-bp VNTR showed significant association with ADHD. They have also examined the haplotype frequencies and biased transmission of one haplotype was observed in ADHD probands. LD analysis showed very strong disequilibrium between exon 1 12-bp duplication and exon 3 48-bp VNTR. Strong LD was also observed between the 5' flanking 120-bp duplication and exon 1 12-bp duplication.

Other variant reported by this study (count: 3)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD4 promoter duplication 120bp	1 repeat/2 repeat		HHRR P-value=0.351, X²=0.87, RR=0.87; TDT P-value...... HHRR P-value=0.351, X²=0.87, RR=0.87; TDT P-value=0.2733, X²=1.2 More...	revealed lack of association	Non-significant
DRD4 exon1 ins/del 12bp	insertion/deletion		HHRR P-value=0.413, X²=0.67, RR=1.17; TDT P-value...... HHRR P-value=0.413, X²=0.67, RR=1.17; TDT P-value=0.3173, X²=1.0 More...	revealed lack of association	Non-significant
DRD4 exon3 VNTR	2 and 4 repeats/6 and 7 repeats		HHRR P-value=0.0301, X²=4.70, RR=1.81; TDT P-valu...... HHRR P-value=0.0301, X²=4.70, RR=1.81; TDT P-value=0.0588, X²=3.57 More...	HHRR analysis showed a significant association; TDT analysis revealed a positive trend towards association	Significant

Genes reported by this study (count: 1)