Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.
The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Felsenstein Medical Research Center, Petah Tikva, Israel. Electronic address: mcarmel@post.tau.ac.il.
Miri
M
Carmel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Child Psychiatry Unit, Edmond and Lily Safra Children's Hospital, Sheba MedicalCenter, Tel Hashomer, Ramat Gan, Israel; Rabin Medical Center, 49100 Petah Tikva, Israel.
Omer
O
Zarchi
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Felsenstein Medical Research Center, Petah Tikva, Israel.
Elena
E
Michaelovsky
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Felsenstein Medical Research Center, Petah Tikva, Israel.
Amos
A
Frisch
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Felsenstein Medical Research Center, Petah Tikva, Israel.
Miriam
M
Patya
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Child Psychiatry Unit, Edmond and Lily Safra Children's Hospital, Sheba MedicalCenter, Tel Hashomer, Ramat Gan, Israel; Nes-Ziyyona-Beer Yaakov Mental Health Center, Beer Yaakov, Israel.
Tamar
T
Green
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Child Psychiatry Unit, Edmond and Lily Safra Children's Hospital, Sheba MedicalCenter, Tel Hashomer, Ramat Gan, Israel.
Doron
D
Gothelf
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Felsenstein Medical Research Center, Petah Tikva, Israel; Geha Mental-Health Center, Petah Tikva, Israel.
Abraham
A
Weizman
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D056344:Executive Function; D020022:Genetic Predisposition to Disease; D006803:Human Development; D006801:Humans; D007360:Intelligence / Q000235:genetics* / Q000502:physiology; D007361:Intelligence Tests; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000235:genetics; D011110:Polymorphism, Genetic; D011394:Proline Oxidase / Q000235:genetics*; D011618:Psychotic Disorders / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics
D011394:Proline Oxidase; C582834:PRODH protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
22q11.2DS; COMT; Executive function (EF); Intelligence quotient (IQ)