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	Mill J, 200312960764
Citation	Mill J., Fisher N., Curran S., Richards S., Taylor E. and Asherson P. (2003) "Polymorphisms in the dopamine D4 receptor gene and attention-deficit hyperactivity disorder." Neuroreport, 14(11): 1463-6.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	188 probands and their families
Predominant Ethnicity

Detail Info

Summary	In this study they have genotyped five polymorphisms (a 120 bp promoter-region duplication, the -616 C/G substitution, the -521C/T substitution, a poly-G repeat in intron 1, and the 48 bp exon 3 repeat) across the gene in a large clinical sample (n=188) and their families. They found that none of the markers is individually associated with ADHD, although there is evidence to suggest that a haplotype of markers in the 5' promoter region of the gene (allele 2 of the 120 bp duplication, the C allele of the -616 substitution, and the C allele of the -521 substitution) may confer susceptibility.
Total Sample	In total, DNA from 188 probands and their families were used for this study. DNA was available from both parents for 121 of the families, and from only the mother in 64 families. At least 1 sibling who was also genotyped was available for 113 of the affected families.
Sample Collection	In total, DNA from 188 probands and their families were used for this study.
Diagnosis Description	Cases were referred for assessment if they were thought by experienced clinicians to have a diagnosis of the combined subtype of ADHD under standard diagnostic criteria, with no significant Axis I co-morbidity apart from oppositional defiant disorder and conduct disorder. Parents of referred cases were interviewed with a modified version of the Child Assessment Parent Interview. Information on ADHD symptoms at school were obtained using the Conners questionnaire. Out of 188 cases included in this study, 176 had the combined subtype, eight had the hyperactive/impulsive subtype and four the inattentive subtype.
Technique	DNA was obtained using buccal swabs as described in Freeman et al. The exon 3 VNTR was amplified as described by Mill et al. and PCR products were run out on a 2% agarose gel stained with ethidium bromide and analysed under u.v. light. The 120 bp promoter duplication was genotyped as described by Seaman et al. and PCR products were run out on a 2% agarose gel stained with ethidium bromide and analysed under u.v. light. The -521 C/T SNP was assayed by digesting the PCR product with 5 units FspI and running out the fragments on a 2% agarose gel stained with ethidium bromide. The -616 C/G SNP was assayed by digesting the PCR product with 5 units BlpI and running out the fragments on a 2% agarose gel stained with ethidium bromide. The intron one poly-G repeat was genotyped as described by Petronis et al.
Analysis Method	Family genotype data was analyzed using David Clayton's program TRANSMIT (version 5.4), which is available for download from the web at http://www. gene.cimr.cam.ac.United Kingdom/clayton/software/. The program Simwalk2 (version 2.83) written by Eric Sobel and available online at http://watson.hgen.pitt.edu/docs/simwalk2.html was used to infer haplotype structure and compute LD relationships between each of the markers.
Result Description	They found that none of the markers is individually associated with ADHD, although there is evidence to suggest that a haplotype of markers in the 5' promoter region of the gene (allele 2 of the 120 bp duplication, the C allele of the -616 substitution, and the C allele of the -521 substitution) may confer susceptibility.

Other variant reported by this study (count: 5)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD4 intron1 (G)n			TRANSMIT P-value>0.05 TRANSMIT P-value>0.05	no evidence of biased transmission to ADHD probands was found	Non-significant
DRD4 exon3 VNTR			TRANSMIT P-value>0.05 TRANSMIT P-value>0.05	no evidence of biased transmission to ADHD probands was found	Non-significant
DRD4 promoter -616C/G	C/G		TRANSMIT P-value>0.05 TRANSMIT P-value>0.05	no evidence of biased transmission to ADHD probands was found	Non-significant
DRD4 promoter -521C/T	C/T		TRANSMIT P-value>0.05 TRANSMIT P-value>0.05	no evidence of biased transmission to ADHD probands was found	Non-significant
DRD4 promoter duplication 120bp			TRANSMIT P-value>0.05 TRANSMIT P-value>0.05	no evidence of biased transmission to ADHD probands was found	Non-significant

Genes reported by this study (count: 1)