title: Association between a common haplotype in the COMT gene region and psychiatric disorders in individuals with 22q11.2DS.
abstract: The 22q11.2 deletion syndrome (22q11.2DS) is the most common hemizygous deletion syndrome in humans. In addition to a wide range of physical abnormalities 22q11.2DS subjects show high prevalence of several psychiatric disorders. In our previous study we showed that the low-activity allele (158Met) of the COMT gene is a risk factor for attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) in 22q11.2DS individuals. In the present study we 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 (OR 3.13, chi2=4.38, p=0.036) and OCD (OR 4.00, chi2=6.41, p=0.011) 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. 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.
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Michaelovsky
authors.forename: Doron
authors.initials: D
authors.lastname: Gothelf
authors.forename: Michael
authors.initials: M
authors.lastname: Korostishevsky
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.forename: Merav
authors.initials: M
authors.lastname: Burg
authors.forename: Miri
authors.initials: M
authors.lastname: Carmel
authors.forename: Tamar
authors.initials: T
authors.lastname: Steinberg
authors.forename: Dov
authors.initials: D
authors.lastname: Inbar
authors.forename: Alan
authors.initials: A
authors.lastname: Apter
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine