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	Domschke K, 200515717295
Citation	Domschke K., Sheehan K., Lowe N., Kirley A., Mullins C., O'Sullivan R., Freitag C., Becker T., Conroy J., Fitzgerald M., Gill M. and Hawi Z. (2005) "Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAO-A 941G allele to affected children." Am J Med Genet B Neuropsychiatr Genet, 134B(1): 110-4.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	179 nuclear families
Predominant Ethnicity	Caucasian
Population	Ireland
Age Group	Children/Adolescents

Detail Info

Summary	They examined four polymorphisms in the MAO-A gene (30 bp promoter VNTR, CA microsatellite in intron 2, 941G/T SNP in exon 8, and A/G SNP in intron 12) as well as two markers in the MAO-B gene (CA microsatellite in intron 2 and T/C SNP in intron 13) for association with ADHD in an Irish sample of 179 nuclear families. TDT analysis of the examined MAO-A markers revealed a significant association of the more active MAO-A 941G allele with the disorder. In addition, haplotype analysis revealed a significantly increased transmission of a haplotype consisting of the shorter allele of the promoter VNTR (allele 1), the 6-repeat allele of the CA microsatellite and the G-allele of the 941G/T SNP to ADHD cases. No significant distortion in the number of transmitted alleles was observed between the two examined MAO-B polymorphisms and ADHD. These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD at least in the Irish population.
Total Sample	The Irish clinical ADHD sample comprising 179 nuclear families was recruited from child psychiatric clinics and schools in West County Dublin and from the Hyperactive and Attention Deficit Children's Support Group of Ireland. Further details on the sample used in the present study can be found in Kirley et al. [2004].
Sample Collection	The Irish clinical ADHD sample comprising 179 nuclear families was recruited from child psychiatric clinics and schools in West County Dublin and from the Hyperactive and Attention Deficit Children's Support Group of Ireland.
Diagnosis Description	Further details on the sample used in the present study can be found in Kirley et al. [2004].
Technique	DNA was extracted from whole blood using standard phenol chloroform procedure or from buccal cells as described in Daly et al. [1999]. Fragments containing the respective polymorphisms were amplified by PCR on a PTC-225 Peltier Thermocycler and subsequently genotyped using the conditions given in the original publication. The two microsatellite markers (MAO-A CA(n) and MAO-B CA(n) (rs3838196)) were genotyped using the semi automated florescent method on an ABI 3100 DNA sequencer (ABI Applied Biosystems, Warrington, United Kingdom).
Analysis Method	For single marker analysis, they used the transmission disequilibrium test (TDT). The McNemar X² test was used to assess the significance level. For the analysis of multi-allelic markers, they applied the ETDT (TDTPHASE v2.40). Hardy-Weinberg equilibrium was examined using the online site (http://kursus.kvl.dk/shares/vetgen/_Popgen/genetik/applets/kitest.htm). Haplotype analysis was carried out using the program FAMHAP (version 14). In this program, an expectation maximization (EM) algorithm is implemented to estimate transmitted and nontransmitted haplotype frequencies. Statistical analyses were not corrected for multiple testing.
Result Description	TDT analysis of the examined MAO-A markers revealed a significant association of the more active MAO-A 941G allele with the disorder (X²=5.1, P=0.03, OR=1.7). In addition, haplotype analysis revealed a significantly increased transmission of a haplotype consisting of the shorter allele of the promoter VNTR (allele 1), the 6-repeat allele of the CA microsatellite and the G-allele of the 941G/T SNP (famhap global statistic 34.54, P=0.01) to ADHD cases. No significant distortion in the number of transmitted alleles was observed between the two examined MAO-B polymorphisms and ADHD.

SNPs reported by this study (count: 3)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs979605	A/G		allelic TDT P-value=0.71, X²=0.2, df=1	did not show any significant distortion in the transmission ...... did not show any significant distortion in the transmission to ADHD cases More...	Non-significant
rs1799836	T/C		allelic TDT P-value=1.0, X²=0, df=1	did not show any significant distortion in the transmission ...... did not show any significant distortion in the transmission to ADHD cases More...	Non-significant
rs3838196			allelic TDT P-value=0.56, LRS=5.8, df=7	did not show any significant distortion in the transmission ...... did not show any significant distortion in the transmission to ADHD cases More...	Non-significant

Other variant reported by this study (count: 3)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
MAOA exon8 941G/T	T/G		allelic TDT P-value=0.03, X²=5.1, df=1; TDT P-val...... allelic TDT P-value=0.03, X²=5.1, df=1; TDT P-value=0.06, X²=4.3 in the sample for parental history of ADHD More...	showed significantly higher transmission of the more active 941G allele to ADHD cases	Significant
MAOA intron2 CA(n)			allelic TDT P-value=0.15, LRS=10.8, df=7 allelic TDT P-value=0.15, LRS=10.8, df=7	did not show any significant distortion in the transmission to ADHD cases	Non-significant
MAOA promoter VNTR			allelic TDT P-value=0.39, X²=0.9, df=1 allelic TDT P-value=0.39, X²=0.9, df=1	did not show any significant distortion in the transmission to ADHD cases	Non-significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
MAOB	no polymorphism was significantly associated with ADHD no polymorphism was significantly associated with ADHD	Non-significant
MAOA	A haplotype containing the shorter 3 allele of the 30 bp VNT...... A haplotype containing the shorter 3 allele of the 30 bp VNTR and allele 6 of the CA-repeat, famhap global statistic: 24.86, P-value=0.05; a haplotype comprising 3 allele of the 30 bp VNTR, allele 6 of the CA-repeat and the 941G allele was preferentially transmitted to ADHD cases famhap global statistic: 34.54, P-value=0.01; suggested the importance of the 941G/T MAO-A polymorphism in the development of ADHD at least in the Irish population. More...	Significant