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	Michaelovsky E, 200817949513
Citation	Michaelovsky E., Gothelf D., Korostishevsky M., Frisch A., Burg M., Carmel M., Steinberg T., Inbar D., Apter A. and Weizman A. (2008) "Association between a common haplotype in the COMT gene region and psychiatric disorders in individuals with 22q11.2DS." Int J Neuropsychopharmacol, 11(3): 351-63.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	55 unrelated 22q11.2DS individuals and 95 of their parents
Predominant Ethnicity	Jews
Population	Israel
Gender	34 males, 21 females
Age Group	Children/Adolescents and Adults : mean age 16.6,SD=10.2 years

Detail Info

Summary	In the present study they have genotyped fifty-five 22q11.2DS individuals and 95 of their parents for eight SNPs in and around the COMT gene. A haplotype composed of three SNPs [rs2097603; rs4680 (158Val/Met) ; rs165599] representing the major linkage disequilibrium blocks in COMT and previously implicated in functional variation, was found to be associated with ADHD and OCD in 22q11.2DS individuals. A common risk haplotype (G-A-A) was significantly associated with both ADHD and OCD in 22q11.2DS individuals. Interestingly, the same haplotype was recently found to be associated with efficient prefrontal performance in the general population. The risk haplotype was not found to be associated with IQ scores in our 22q11.2DS sample. Parental origin of the deletion did not affect the susceptibility to ADHD and OCD in the 22q11.2DS subjects.
Total Sample	Fifty-five unrelated 22q11.2DS individuals referred to the Neurobehavioral Genetics Clinic of the Feinberg Child Study Center, Schneider Children's Medical Center of Israel, described in our previous study (Gothelf et al., 2006), and 95 of their parents were included in this study (mean ages 16.6, SD=10.2 yr, 34 males, 21 females).
Sample Collection	Jewish ethnic background
Diagnosis Description	Description of diagnostic tools (K-SADS-PL; SCID-P structured interviews) and full-scale, verbal and performance IQ tests (FSIQ, VIQ and PIQ) applied to the 22q11.2DS participants is provided elsewhere (Gothelf et al., 2006). Inclusion criteria were: a proven 22q11.2 deletion, confirmed by fluorescent in-situ hybridization (FISH) using a commercial probe, and age >6 years. Of the 55 individuals with 22q11.2DS 23 (41.8%) met DSM-IV criteria for ADHD, 14 (25.5%) for OCD and seven (12.7%) for both ADHD and OCD. Five subjects (9.1%) met DSM-IV criteria of SZ/SZaff disorder. Two of them had comorbid OCD and two had history of ADHD.
Technique	DNA was extracted by a commercial kit (Roche Diagnostics, Mannheim, Germany) from 8 ml venous blood. Primers for all markers and PCR reaction are described in detail in the original publication.
Analysis Method	Haplotype and allelic distribution of the eight SNP loci were determined by direct counting in the hemizygote subjects. Possible differences in the frequency of haplotypes or alleles between the samples were calculated using the X² test. The Bonferroni correction was performed by the SISA online procedure (http://home.clara.net/ sisa/bonfer.htm).
Result Description	This study demonstrated the association of a particular COMT haplotype with susceptibility to both ADHD and OCD in 22q11.2DS and supports the hypothesis that COMT gene variations contribute to genetic predisposition to psychiatric disorders in the general population.

SNPs reported by this study (count: 8)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs4818	C/G		P-value=0.005, X²(1)=7.77	showed significant association with ADHD showed significant association with ADHD	Significant
rs4680	G/A		P-value=0.005, X²(1)=7.77	showed significant association with ADHD showed significant association with ADHD	Significant
rs4633	C/T		P-value=0.005, X²(1)=7.77	showed significant association with ADHD showed significant association with ADHD	Significant
rs3838146	insC/delC		P-value=0.012, X²(1)=6.37	showed significant association with ADHD showed significant association with ADHD	Significant
rs2240717	T/C		X²(1)=0.34	no significant association no significant association	Non-significant
rs2073748	C/T		X²(1)=0.34	no significant association no significant association	Non-significant
rs2075507	A/G		P-value=0.045, X²(1)=4.04	showed significant association with ADHD showed significant association with ADHD	Significant
rs165599	A/G		P-value=0.02, X²(1)=5.44	showed significant association with ADHD showed significant association with ADHD	Significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
ARVCF	8-SNP COMT-ARVCF haplotype G-T-C-A-insC-A-C-T P-value=0.017,...... 8-SNP COMT-ARVCF haplotype G-T-C-A-insC-A-C-T P-value=0.017, OR 7.30, X² (1)=5.74; 8-SNP COMT-ARVCF haplotype A-C-G-G-delC-G-C-T P-value=0.012, OR 0.13, X² (1)=6.37; associated with ADHD More...	Significant
COMT	haplotype G-A-A P-value=0.036, OR=3.13, X² (1)=4....... haplotype G-A-A P-value=0.036, OR=3.13, X² (1)=4.38; haplotype A-G-G P-value=0.006, OR=0.12, X² (1)=7.71; 8-SNP COMT-ARVCF haplotype G-T-C-A-insC-A-C-T P-value=0.017, OR 7.30, X² (1)=5.74 ; 8-SNP COMT-ARVCF haplotype A-C-G-G-delC-G-C-T P-value=0.012, OR=0.13, X² (1)=6.37; associated with ADHD More...	Significant