Study Report
Basic Info
Reference |
Michaelovsky E, 200817949513
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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.
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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
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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 |
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P-value=0.005, X2(1)=7.77 |
showed significant association with ADHD
showed significant association with ADHD
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Significant
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rs4680 |
G/A |
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P-value=0.005, X2(1)=7.77 |
showed significant association with ADHD
showed significant association with ADHD
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Significant
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rs4633 |
C/T |
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P-value=0.005, X2(1)=7.77 |
showed significant association with ADHD
showed significant association with ADHD
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Significant
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rs3838146 |
insC/delC |
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P-value=0.012, X2(1)=6.37 |
showed significant association with ADHD
showed significant association with ADHD
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Significant
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rs2240717 |
T/C |
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X2(1)=0.34 |
no significant association
no significant association
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Non-significant
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rs2073748 |
C/T |
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X2(1)=0.34 |
no significant association
no significant association
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Non-significant
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rs2075507 |
A/G |
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P-value=0.045, X2(1)=4.04 |
showed significant association with ADHD
showed significant association with ADHD
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Significant
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rs165599 |
A/G |
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P-value=0.02, X2(1)=5.44 |
showed significant association with ADHD
showed significant association with ADHD
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Significant
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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...
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Significant
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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...
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Significant
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