title: Pilot study on HTR2A promoter polymorphism, -1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive-compulsive disorder.
abstract: A previous study showed that a single nucleotide polymorphism (SNP), -1438G/A (rs6311), found in the transcriptional control region of the gene that encodes the serotonin-receptor 2A (HTR2A) was associated with obsessive-compulsive disorder (OCD) in a sample of children and adolescents. In this study, we reanalyzed the association of this SNP with OCD in an enlarged population of 136 cases (55 previous + 81 new cases) and compared them to 106 newly recruited, healthy, age-matched controls. We also investigated whether this SNP or its copy number variations (CNV) was associated with OCD severity and age of onset. The CNV was analyzed in a DNA region located near rs6311. The results confirmed the association between the A-allele and early onset OCD in children and adolescents, with an odds ratio (OR) of 1.69 [95% CI (1.17, 2.46); p = 0.005]. Strikingly, we found that carriers of one copy (deletion) of the CNV were associated with a very early onset OCD (2.5 years earlier than the typical onset), and they had increased CY-BOCS scores (8.7 points higher compared to "normal" CNV and duplications); which is related to increased severity of OCD symptoms (p = 0.031; p = 0.004, respectively). Compared to the normal CNV and duplications, the association between the deletion and OCD showed an OR of 7.56 [95% CI (1.32, 142.84); p = 0.020]. These results pointed to the functional importance of this promoter region of HTR2A; it influenced the occurrence, the onset, and the severity of OCD.
authors.affiliation: Hospital of Child and Adolescent Psychiatry, University of Zurich, Neumuensterallee 9, 8032, Zurich, Switzerland. Susanne.walitza@kjpdzh.ch
authors.forename: Susanne
authors.initials: S
authors.lastname: Walitza
authors.forename: Daniel Sabanés
authors.initials: DS
authors.lastname: Bové
authors.forename: Marcel
authors.initials: M
authors.lastname: Romanos
authors.forename: Tobias
authors.initials: T
authors.lastname: Renner
authors.forename: Leonhard
authors.initials: L
authors.lastname: Held
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
authors.forename: Christoph
authors.initials: C
authors.lastname: Wewetzer
authors.forename: Christian
authors.initials: C
authors.lastname: Fleischhaker
authors.forename: Helmut
authors.initials: H
authors.lastname: Remschmidt
authors.forename: Andreas
authors.initials: A
authors.lastname: Warnke
authors.forename: Edna
authors.initials: E
authors.lastname: Grünblatt
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A