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	Todd RD, 2001(b)11449395
Citation	Todd R. D., Neuman R. J., Lobos E. A., Jong Y. J., Reich W. and Heath A. C. (2001) "Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes in a population sample of twins." Am J Med Genet, 105(5): 432-8.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	523 families with 1045 genotyped twins
Predominant Ethnicity	USA
Population	USA
Gender	53.7% male
Age Group	Children/Adolescents : 7-19 years

Detail Info

Summary	In this report, they test for the possible association of these two polymorphisms with population-derived samples of DSM-IV ADHD subtypes. Furthermore, they extend previous studies by testing for associations with ADHD subtypes derived from latent-class analysis of interview responses. In contrast to most, but not all, previous studies, they failed to demonstrate any significant association of the exon 3 7-repeat allele with ADHD. Nor did they replicate the association of the 5' 120 base pair repeat polymorphism. They do find a significant association of the exon 3 3-repeat allele with a novel talkative/impulsive latent-class-defined subtype of ADHD.
Total Sample	For the current study, DNA samples from the first 523 families with complete diagnostic information as well as blood samples were included. This included 110 random control families and 413 families in which at least one twin had passed the screening interview criterion. Of the 1045 genotyped twins, 53.7% were male, 1/3 were monozygotic, and the remainder were same-sex or opposite-sex dizygotic pairs. This included 219 individuals who qualified for a DSM-IV ADHD diagnosis (inattentive, n=124; combined, n=78; hyperactive/impulsive, n=17).
Sample Collection	The details of the recruitment strategy and representativeness of the individuals participating in this study have been previously described [Hudziak et al., 2000].
Diagnosis Description	Briefly, twins of age 7-19 years were identified by a two-stage process. A parent completed a brief phone interview about their twins, which included screening questions about inattentive ADHD symptoms in the present or past. Families for which at least one twin had three or more past or present inattentive ADHD symptoms as well as a group of randomly selected families were invited to complete full diagnostic evaluations. These included a DSM-IV-modified Diagnostic Interview for Children (called the MAGIC [Reich, 2000] and a variety of parent/teacher report questionnaires as well as cognitive and educational achievement testing. A parent (the mother 94% of the time) completed a diagnostic interview for each twin and the twins completed interviews about themselves. Zygosity was determined using a standard series of zygosity questions and checked using a panel of DNA markers.
Technique	Venous blood samples were collected from both biological parents and twins. Genotyping of the polymorphisms was done as described by others with minor modifications (5' 120 base pair repeat polymorphism [Seaman et al., 1999]; exon 3 48 base pair repeat VNTR [LaHoste et al., 1996]). The population allele frequencies were determined by FBAT [Laird et al., 2000] for each polymorphism and haplotype.
Analysis Method	The ETDT software program of Sham and Curtis [1995] was used for all analyses. The ETDT uses a logistic regression model to test the null hypothesis of equal transmission of all alleles by heterozygous parents. The ETDT also compares the number of times a given allele is transmitted from a heterozygous parent to the affected offspring versus how many times it is not transmitted, thereby performing a traditional TDT test [Spielman et al., 1993].
Result Description	In contrast to most, but not all, previous studies, they failed to demonstrate any significant association of the exon 3 7-repeat allele with ADHD. Nor did they replicate the association of the 5' 120 base pair repeat polymorphism. They do find a significant association of the exon 3 3-repeat allele with a novel talkative/impulsive latent-class¨Cdefined subtype of ADHD.

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD4 promoter duplication 120bp			ETDT P-value=0.47, X²(2df)=1.5 in DSM-IV inattent...... ETDT P-value=0.47, X²(2df)=1.5 in DSM-IV inattentive, ETDT P-value=0.50, X²(1df)=0.4 in DSM-IV combined, ETDT P-value=1.00, X²(1df)=0 in DSM-IV hyperactive/impulsive, ETDT P-value=0.38, X²(2df)=2.0 in DSM-IV any ADHD; allele-wise P-value=0.44, corrected P-value=0.69 for Allele 1, allele-wise P-value=0.39, corrected P-value=0.63 for Allele 2 in DSM-IV any ADHD; allele-wise P-value=0.71, corrected P-value=0.92 for Allele 1, allele-wise P-value=0.63, corrected P-value=0.86 for Allele 2 in DSM-IV inattentive; allele-wise P-value=0.51, corrected P-value=0.76 for Allele 1 and Allele 2 in DSM-IV combined; allele-wise P-value=1.00, corrected P-value=1.00 for Allele 1 and Allele 2 in DSM-IV hyperactive/impulsive More...	there was no evidence for biased transmission of any allele for either polymorphism for the DSM-IV-defined ADHD subtypes	Non-significant
DRD4 exon3 VNTR			ETDT P-value=0.86, X²(7df)=3.3 in DSM-IV inattent...... ETDT P-value=0.86, X²(7df)=3.3 in DSM-IV inattentive, ETDT P-value=0.12, X²(6df)=10.0 in DSM-IV combined, ETDT P-value=0.60, X²(5df)=3.7 in DSM-IV hyperactive/impulsive, ETDT P-value=0.81, X²(7df)=3.8 in DSM-IV any ADHD; allele-wise P-value=0.41, corrected P-value=0.93 for Allele 2, allele-wise P-value=1.00, corrected P-value=1.00 for Allele 3, allele-wise P-value=0.58, corrected P-value=0.99 for Allele 4 and Allele 7, allele-wise P-value=0.21, corrected P-value=0.68 for Allele 8 in DSM-IV any ADHD; allele-wise P-value=0.29, corrected P-value=0.81 for Allele 2, allele-wise P-value=0.29, corrected P-value=0.82 for Allele 3, allele-wise P-value=0.47, corrected P-value=0.96 for Allele 4, allele-wise P-value=0.55, corrected P-value=0.98 for Allele 7, allele-wise P-value=1.00, corrected P-value=1.00 for Allele 8 in DSM-IV inattentive; allele-wise P-value=0.82, corrected P-value=1.00 for Allele 2, allele-wise P-value=0.10, corrected P-value=0.33 for Allele 3, allele-wise P-value=0.89, corrected P-value=1.00 for Allele 4, allele-wise P-value=1.00, corrected P-value=1.00 for Allele 7 in DSM-IV combined; allele-wise P-value=0.44, corrected P-value=0.68 for Allele 4, allele-wise P-value=0.53, corrected P-value=0.77 for Allele 7 in DSM-IV hyperactive/impulsive More...	there was no evidence for biased transmission of any allele for either polymorphism for the DSM-IV-defined ADHD subtypes	Non-significant

Genes reported by this study (count: 1)