a1 Felsenstein Medical Research Center, Rabin Medical Center, Petah Tiqwa, Israel
a2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
a3 The Neurogenetics Center, Feinberg Child Study Center, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel
a4 Sackler Faculty of Medicine, Department Anatomy and Anthropology, Tel Aviv University, Tel Aviv, Israel
a5 Research Unit, Geha Mental Health Center, Petah Tiqwa, Israel
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, χ2=4.38, p=0.036) and OCD (OR 4.00, χ2=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.
(Received May 10 2007)
(Reviewed June 13 2007)
(Revised July 08 2007)
(Accepted August 21 2007)
(Online publication October 22 2007)
c1 Address for correspondence: A. Frisch, Ph.D., Felsenstein Medical Research Center (FMRC), Rabin Medical Center, Petah Tiqwa 49100, Israel. Tel.: 972-3-9376762 Fax: 972-3-9211478 E-mail: email@example.com
* Both authors contributed equally to this work.