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	Johansson S, 200818081165
Citation	Johansson S., Halleland H., Halmoy A., Jacobsen K. K., Landaas E. T., Dramsdahl M., Fasmer O. B., Bergsholm P., Lundervold A. J., Gillberg C., Hugdahl K., Knappskog P. M. and Haavik J. (2008) "Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1470-5.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	358 ADHD patients and 340 healthy controls
Predominant Ethnicity	Caucasian
Population	Norway
Gender	182 males and 176 females for cases, 157 males and 183 females for controls
Age Group	Adults : >18 years

Detail Info

Summary	In this study of adults with ADHD, they evaluated the three most commonly studied ADHD candidate genetic polymorphisms; the dopamine receptor D4 (DRD4) exon 3 VNTR repeat, a microsatellite repeat 18.5 kb upstream of the DRD5 locus and the 3' UTR dopamine transporter SLC6A3 (DAT 1) VNTR. They examined 358 clinically diagnosed adult Norwegian ADHD patients (51% males) and 340 ethnically matched controls. They found a nominally significant overall association with adult ADHD for the DRD5 microsatellite marker (P-value=0.04), and a trend toward increased risk associated with the 148-bp allele consistent with recent meta-analyses. The strongest overall association (P-value=0.02) and increased risk for the 148-bp allele [odds ratio (OR)=1.27 (95% CI: 1.00-1.61)] were seen in the inattentive and combined inattentive/hyperactive group as previously reported for childhood ADHD. No association was found for the DRD4 or SLC6A3 polymorphisms in this patient sample.
Total Sample	the total sample consists of 358 ADHD patients (182 males and 176 females) and 340 (157 males and 183 females) ethnically matched healthy controls (198 blood donors and 142 healthy volunteers)
Sample Collection	white adults of Norwegian ancestry
Diagnosis Description	ASRS is a short screening scale for use in the general population.The Norwegian version of the ASRS is a translation of the original scale and consists of 18 questions that follow the DSM-IV-TR criteria for ADHD. Nine questions address the frequency of inattentive symptoms, and nine address the frequency of hyperactivity symptoms. The participants indicate how often symptoms occur by using a Likert scale of 0-4 (0=never, 1=seldom, 2=sometimes, 3=often, 4=very often). This method was used in the present study to determine the levels of ADHD symptoms during the past 6 months and to classify the patients according to DSM-IV subtypes.
Technique	Genomic DNA was extracted either from whole blood, or from saliva using the OrageneTM DNA Self-Collection Kit from DNA Genotek at the HUNT biobank. DNA from cases and controls was diluted to a final concentration of 10 ng/ul before distributed to 96 well plates. Cases and controls were mixed with a minimum of two internal controls and two blank samples on each plate. In short, to reduce the risk of erroneous genotyping due to differential amplification of the repeats, all reverse primers were fluorescently labeled and PCR products were visualized on an ABI 3100 sequencer and automatically called using the GeneMapper software.
Analysis Method	Allele frequencies and the overall likelihood ratio test for each marker were calculated using the UNPHASED software [Dudbridge, 2006] which allows testing of multi-allelic markers. A simple 2x2 Chi-square test was used to compare the allelic odds between the 'atrisk-allele' versus all other alleles at each marker.
Result Description	They found a nominally significant overall association with adult ADHD for the DRD5 microsatellite marker (P-value=0.04), and a trend toward increased risk associated with the 148-bp allele consistent with recent meta-analyses. The strongest overall association (P-value=0.02) and increased risk for the 148-bp allele [odds ratio (OR)=1.27 (95% CI: 1.00-1.61)] were seen in the inattentive and combined inattentive/hyperactive group as previously reported for childhood ADHD. No association was found for the DRD4 or SLC6A3 polymorphisms in this patient sample.

Other variant reported by this study (count: 3)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD5 5'-flanking (CT/GT/GA)n			Overall P-value=0.04; allelic P-value=0.09, OR=1.20; overall...... Overall P-value=0.04; allelic P-value=0.09, OR=1.20; overall P-value=0.02, OR=1.27 in the inattentive or combined inattentive/hyperactive subtypes; overall P-value=0.04 for male patients More...	nominally significant association	Significant
SLC6A3 3'-UTR VNTR			Overall P-value=0.48; allelic P-value=0.59, OR=0.94 Overall P-value=0.48; allelic P-value=0.59, OR=0.94	showed no association	Non-significant
DRD4 exon3 VNTR			Overall P-value=0.31; allelic P-value=0.27, OR=0.90 Overall P-value=0.31; allelic P-value=0.27, OR=0.90	showed no association	Non-significant

Genes reported by this study (count: 3)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
DRD4	no association between ADHD and the DRD4 polymorphism no association between ADHD and the DRD4 polymorphism	Non-significant
DRD5	a nominally significant overall association between ADHD and...... a nominally significant overall association between ADHD and the DRD5 microsatellite marker More...	Significant
SLC6A3	no association between ADHD and the SLC6A3 polymorphism no association between ADHD and the SLC6A3 polymorphism	Non-significant